-Bronchoalveolar lavage fluid (BALF) is commonly examined for pulmonary toxicity in animal studies. Two common means of anesthesia before euthanasia and bronchoalveolar lavage in rats are intraperitoneal injection of pentobarbital and inhalation of isoflurane. Medetomidine-midazolambutorphanol is an alternative anesthesia to pentobarbital for animal welfare; however, the effect of this combination on BALF and blood chemistry is unknown. Here, we compared the effects of anesthesia by intraperitoneal injection of pentobarbital or one of two combinations of medetomidine-midazolambutorphanol (dose, 0.375-2.0-2.5 or 0.15-2.0-2.5 mg/kg) or by inhalation of isoflurane on BALF and blood chemistry in rats with or without pulmonary inflammation. In BALF, we determined total protein, albumin, lactate dehydrogenase, total cell count and neutrophil count. In serum, we conducted a general chemistry screen. After anesthesia with pentobarbital or isoflurane, there were no significant differences between any of the BALF or blood chemistry parameters with or without inflammation. After anesthesia with either of the combinations of medetomidine-midazolam-butorphanol, lactate dehydrogenase, total cell count, neutrophil count, and almost all of the blood chemistry parameters were comparable with those observed after pentobarbital or isoflurane; however, BALF albumin and serum glucose were significantly increased in rats without inflammation. After the combination of low-dose medetomidine in rats with inflammation, BALF parameters were comparable with those observed after pentobarbital or isoflurane. Our results show that, of the anesthetics examined, inhalation of isoflurane is the most appropriate means of anesthesia when examining BALF or serum for toxicity studies in rats.
Photosensitive solid-liquid compounds were fabricated by filling nanoholes of alumina or polymer films with dye solution. Although these compounds can be handled as solid in device fabrication processes, the liquid phase inside 50–200nm holes provides a sufficient free volume for photochromic dye to change molecular structure. Nanoholes also prevent the solution to flow disturbing an optically written image. A function of the rewritable grating was demonstrated by bleaching a polycarbonate-based compound with various interference fringes of green laser.
An approach to predicting the bioconcentration factor (BCFpre ) from the predicted uptake rate constant (k1 pre ) and the depuration rate constant measured in the dietary exposure bioaccumulation fish test (k2 dietary ) [BCFpre = k1 pre /k2 dietary ] is proposed in test guideline 305 of the Organization for Economic Cooperation and Development Guidelines for Testing of Chemicals. Data were collected on the BCFs of 197 test chemicals from Japan's Chemical Substances Control Law database. To demonstrate how the BCFpre compares with experimentally derived BCF under optimum conditions, 48 of 197 test chemicals, including a number of studies that could be considered problematic, were excluded from the analysis. The k1 pre was calculated by using 22 published prediction methods: the correlations between experimental uptake rate constants (k1 aqueous ) and k1 pre for all prediction methods were very low and were statistically nonsignificant (p > 0.05). Three prediction methods were also selected that gave relatively good values for the geometric mean of k1 pre /k1 aqueous and calculated values of BCFpre for 12 test chemicals. Linear relationships (p < 0.05) are presented between logarithm of experimental and predicted BCF. The correlation coefficients of growth-corrected experimental and predicted BCF tended to be higher than values that were not growth corrected. For some test chemicals, use of predicted BCF led to a bioaccumulation classification different from that of existing regulatory criteria.
A potentially useful means of predicting the pulmonary risk posed by new forms of nano-structured titanium dioxide (nano-TiO2) is to use the associations between the physicochemical properties and pulmonary toxicity of characterized forms of TiO2. In the present study, we conducted intratracheal administration studies in rats to clarify the associations between the physicochemical characteristics of seven characterized forms of TiO2 and their acute or subacute pulmonary inflammatory toxicity. Examination of the associations between the physicochemical characteristics of the TiO2 and the pulmonary inflammatory responses they induced revealed (1) that differences in the crystallinity or shape of the TiO2 particles were not associated with the acute pulmonary inflammatory response; (2) that particle size was associated with the acute pulmonary inflammatory response; and (3) that TiO2 particles coated with Al(OH)3 induced a greater pulmonary inflammatory response than did non-coated particles. We separated the seven TiO2 into two groups: a group containing the six TiO2 with no surface coating and a group containing the one TiO2 with a surface coating. Intratracheal administration to rats of TiO2 from the first group (i.e., non-coated TiO2) induced only acute pulmonary inflammatory responses, and within this group, the acute pulmonary inflammatory response was equivalent when the particle size was the same, regardless of crystallinity or shape. In contrast, intratracheal administration to rats of the TiO2 from the second group (i.e., the coated TiO2) induced a more severe, subacute pulmonary inflammatory response compared with that produced by the non-coated TiO2. Since alteration of the pulmonary inflammatory response by surface treatment may depend on the coating material used, the pulmonary toxicities of coated TiO2 need to be further evaluated. Overall, the present results demonstrate that physicochemical properties may be useful for predicting the pulmonary risk posed by new nano-TiO2 materials.
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