Annual Meeting of the Japanese Society of Toxicology

In GLP safety assessment studies, by comparison to other route of administration, inhalation can exhibit a relatively high level of variation in dosage due to the intrinsic characteristics of inhalation study technology. To generate aerosols, different air flow rates must be carefully and consistently controlled. Any change of air flow will cause instant changes of aerosol concentration leading to variation of dosage received by the animal. Most Inhalation delivery systems require a high level of manual intervention to control and adjust air flow; monitoring of the system is manual and often not continuous. This approach is both labor intensive and liable to mistakes. It also lacks precision. An important issue for study integrity is that if the air flow is not continuously monitored and a record maintained, the dosing process becomes a kind of “black box”. Any variation of the flow rate may not be identified immediately resulting in an inability to quantify the extent of a deviation, and leading to GLP compliance problems. Our inhalation system applies an automated control and recording system, which allow us to control, continuously monitor, and retain raw data of all exposure parameters for air flow and concentration of oxygen, carbon dioxide, temperature, humidity throughout the aerosol exposure process. The system will alarm, immediately prompting remedial/corrective action, should any parameter go out of pre-specified range and maintain an audit trail of this. This type of automated inhalation delivery system results in better animal welfare, more complete and reliable study data and excellent GLP compliance.

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Risk assessment of chemical is a key knowledge for the protection of human health. The aim of this study was to establish online course for the self-study of chemical risk assessment. The course outline was divided into 5 lessons consisting of hazard identification, hazard characterization, exposure assessment, and risk characterization. The audio lectures attached with reading materials were added in each lesson. The online qualitative and quantitative course data were evaluated by learners in term of self-learner’s performance and their satisfaction. The demographic data of 20 learners, who enrolled in our course aged between 20 – 30 years old, were post-graduate degree students. Based on the data, 50% of learners rated “fair” about their background knowledge in chemical risk assessment, whereas 25% learners rated “good” and 20% rated “no”. Learners’ satisfaction and their achievement in lesson were rated on a scale 1 (very poor) to 4 (very satisfied). For satisfaction, 65% of the learners rated a “3” for lesson’s style, 55% of the learners rated “3” for interested topics, and 50% of learners rated “4” for time of study. For their achievement in issues, 65% learners had more experience after finishing the course and rated as “4”, 50% learners rated “4” for comprehensive topics, and 55% learners rated quality of the lessons as “4”. Fifty percent learners rated “4” for the application to their career. We concluded that 80% of learners were satisfied in E-training course. Therefore, the online course for risk assessor should be further developed.

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The efficiency of nutrients from Moringa oleifera Lam to prevent the inflammation and tumorigenesis has been reported previously. Therefore, the aim of this study was to investigate the effect of boiled Moringa oleifera Lam. pod (bMO) on the apoptotic pathway related to colon carcinogenesis. Mice were randomly divided into five groups (8 mice/group). Four groups were induced by azoxymethane (AOM, 10 mg/kgBW i.p. at the 3^rd week) followed by dextran sodium sulphate for 7 days (DSS, 2% in drinking water at the 4^th week) and a negative group received AIN-76A basal diet without AOM/DSS induction. Positive control group received basal diet with AOM/DSS induction while the treatment groups received AIN-76A containing 1.5%, 3.0% and 6.0% of bMO at the 1^st week toward the 6^th week before AOM/DSS inductions. Mice were then sacrificed and necropsied at the end of the 20^th week. Pro-apoptosis BAX and anti-apoptosis BCL-2 proteins were investigated by immunohistochemistry. The results showed no significant difference (p<0.05) in all the treatment groups when comparing with the AOM/DSS group. All the treatment groups were not found in the ratio of BAX/BCL-2 and the nuclear staining determined the apoptotic bodies. The study did not indicated clearly the potential effect of bMO to induce apoptosis for colon cancer prevention. However, we can conclude that bMO could reduce the risk of colon cancer by other pathways, but not through the apoptosis process.

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MSI, known to bring molecular distribution information, allows quantification. This has been established with QWBA but it lacks the ability to differentiate between drug components&establish separate quantitative results for each target.This demonstrates our capabilities as complementary to QWBA to follow chloroquine&its metabolites at different time-points after an administration of a radiolabeled dose to rats; euthanized at 4,24,72,168&336h post-dose.Carcasses were frozen in a hexane/dry ice bath,embedded in chilled carboxymethylcellulose&frozen into blocks. QWBA images were obtained following exposure to phosphorimaging screens&scanned using a GE Typhoon scanner. QWBA images were quantified against 14Cfortified standards using MCIDTM. For QMSI, MALDI matrix spiked with labeled chloroquine-d4&its metabolite desethyl chloroquine-d4 were sprayed onto the slide. Analyses were performed by a MALDI-FTICR in the head:the eye& in the mid whole-body region. 1H-Chloroquine&1H-desethyl chloroquine were detected by MALDI-FTICR in the eye: uveal tract, vitreous humor...In the mid whole-body region, 2compounds were detected in organs from T4h sections.2compounds were co-localized into the tissue sections&distributions matched the zones obtained by QWBA.The advantage’s the ability to discriminate between parent drug 1H-choloroquine&its metabolite 1H-desethyl chloroquine so that each compound had its own distribution image&its quantification data.The used labeled forms of both compounds during the matrix deposit allowed normalizing the data for each position with the MALDI onto the section of interest&calibration range of both 1H-choloroquine&1H-desethyl chloroquine and quantifying each compound into the organs of interest with the ILC.QMSI demonstrate the disappearance of the drug &its metabolite with time to understand differential pharmacokinetic demonstrating the additional input of the technology compared to QWBA.

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