Acute and subchronic oral toxicity assessments of BTL tea in experimental animals

Tobacco smoking remains a leading cause of preventable diseases and premature death in many countries. Many smokers want to quit smoking but are not offered the highly effective treatments available to manage tobacco dependency. There has been a current trend for researchers to find new natural ingredients that were safe and still effective in treating tobacco dependence. BTL tea was a herbal-derived product prepared from Herba Menthae, Pogos cablin (Blanco) Benth., Zingiber Officinale Rosc., Flos Chrysanthemi, Radix Glycyrrhizae, Pericarpium Citri deliciosa, and Flos Lonicera. At this time, the safety of this product has not been reported. Thus, this study aimed to evaluate BTL tea’s acute and subchronic toxicity through oral administration in experimental animals. The acute toxicity was determined by Litchfield-Wilcoxon method in mice at the doses of 45.0 g/kg b.w/day to 112.5 g/kg b.w/day. The subchronic toxicity was evaluated following WHO and OECD’s Guidelines in rats with oral doses of 1.08 g/kg b.w/day (equal to recommended human dose) and 3.24 g/kg b.w/day (three times as high as recommended human dose) for four consecutive weeks. As a result, in the acute toxicity test, the mice showed no abnormal sign or death. The subchronic toxicity test, hematological indexes, hepato-renal functions, and microscopic images of liver and kidney were unchanged. However, compared with the control group, there were significant differences in various indexes, including total WBC, lymphocytes, neutrophils, and AST level, but the levels were still safe. In conclusion, BTL tea does not appear to produce acute and subchronic toxicities in mice and rats.

The evaluation of acute and subchronic toxicities of An Phu Khang capsules in experimental animals

The purpose of this research was to evaluate the acute and subchronic toxicities of An Phu Khang capsules through oral administration in experimental animals. The acute toxicity was determined by the method of Litchfield Wilcoxon in Swiss mice. The subchronic toxicity was evaluated by the recommendation of WHO in Wistar rats at these doses of 0.54 g/kg b.w/day (equal to recommended human dose) and 1.62 g/kg b.w/day (3 times as high as recommended human dose) in 4 consecutive weeks. As a result, An Phu Khang capsules at the highest dose used for mice (36.29 g/kg b.w) did not show acute toxicity in mice. In terms of the subchronic toxicity test, after oral administration of An Phu Khang capsules, hematological parameters, hepato-renal functions, and microscopic images of liver and kidney at both doses were unchanged compared with the control group. In conclusion, An Phu Khang with both doses 0.54 g/kg b.w/day and 1.62 g/kg b.w/day did not produce acute and subchronic toxicities in Swiss mice and Wistar rats.

The study of acute and subchronic toxicities of Da Dai Trang HVD capsules in experimental animals

The purpose of this research is to evaluate the acute and subchronic toxicities of DA DAI TRANG HVD capsules through oral administration in experimental animals. The acute toxicity was determined by the method of Litchfield Wilcoxon in Swiss mice. The subchronic toxicity was evaluated by the recommendation of WHO and OECD in Wistar rats with oral doses of 1.44 g/kg/day (equal to recommended human dose) and 4.32 g/kg/day (3 times as high as recommended human dose) in 4 consecutive weeks. As a result, DA DAI TRANG HVD capsules at the highest dose used for mice (99.9 g materials/kg) did not express acute toxicity in mice. In term of the subchonic toxicity test, DA DAI TRANG HVD had no deleterious effect on hematological parameters, hepato-renal functions, macroscopic and microscopic images of livers and kidneys of rats. In conclusion, DA DAI TRANG HVD capsules did not produce the acute and subchronic toxicities in Swiss mice and Wistar rats.

Sub-chronic oral toxicity study of “Phong Thap Dan” tablets in experimental animal

The present study aimed to investigate the sub-chronic toxicity of “Phong thap dan” (PTD) tablets through oral administration in experimental animal. The sub-chronic toxicity was evaluated by the WHO recommendation in Wistar rats at doses of 0.72 g/kg/day (equal to recommended human dose) and 2.16 g/kg/day (3 times as high as recommended human dose). In the sub-chronic experimental group, the PTD was administered orally daily for 8 consecutive weeks. In the evaluation of sub-chronic toxicity, there were no behavioral and physiological change or sign of toxicity. The result of the hematological and biological parameters after administration of PTD tablets showed no change. The histopathology analysis of livers and kidneys indicated that no significant difference was observed between the exposed and unexposed rat groups. In conclusion, “Phong thap dan” tablets did not produce sub-chronic toxicity in Wistar rats.

Sub-chronic oral toxicity study of “Kien Nao Dan” tablets in experimental animal

“Kien nao dan” (KND) tablet is composed of 13 traditional medicines that may has preventive and effective treatment of cerebral ischemia. However, there are no scientific reports of its toxicological properties which guarantee of the safety its usage treatment. Therefore, the aim of this study was to investigate the sub-chronic toxicity of KND tablet on rats through oral administration. The sub-chronic toxicity was evaluated by the recommendation of WHO in Wistar rats at doses of 0.72 g/kg/day (equal to recommended human dose) and 2.16 g/kg/day (3 times as high as recommended human dose) for 8 consecutive weeks. In the evaluation of sub-chronic toxicity, there were no behavioral and physiological changes or signs of toxicity. The result of the hematological and biological parameters after administration of KND tablets showed no change. The histopathologic analysis of livers and kidneys indicated that no significant differences were observed between the exposed and unexposed rat groups. In conclusion, “Kien nao dan” tablets did not produce sub-chronic toxicity in Wistar rats.

A Novel Approach for Quantifying the Pharmacological Activity of T-Cell Engagers Utilizing In Vitro Time Course Experiments and Streamlined Data Analysis

CD3-bispecific antibodies are a new class of immunotherapeutic drugs against cancer. The pharmacological activity of CD3-bispecifics is typically assessed through in vitro assays of cancer cell lines co-cultured with human peripheral blood mononuclear cells (PBMCs). Assay results depend on experimental conditions such as incubation time and the effector-to-target cell ratio, which can hinder robust quantification of pharmacological activity. In order to overcome these limitations, we developed a new, holistic approach for quantification of the in vitro dose–response relationship. Our experimental design integrates a time-independent analysis of the dose–response across different time points as an alternative to the static, “snap-shot” analysis based on a single time point commonly used in dose–response assays. We show that the potency values derived from static in vitro experiments depend on the incubation time, which leads to inconsistent results across multiple assays and compounds. We compared the potency values from the time-independent analysis with a model-based approach. We find comparably accurate potency estimates from the model-based and time-independent analyses and that the time-independent analysis provides a robust quantification of pharmacological activity. This approach may allow for an improved head-to-head comparison of different compounds and test systems and may prove useful for supporting first-in-human dose selection.

Efficacy and immunogenicity of different BCG doses in BALB/c and CB6F1 mice when challenged with H37Rv or Beijing HN878

Two strains of mice (BALB/c and CB6F1) were vaccinated with a range of Bacille Calmette-Guérin (BCG) Danish doses from 3 × 105 to 30 CFU/mouse, followed by aerosol infection with Mtb (H37Rv or West-Beijing HN878 strain). The results indicated that both strains of mice when infected with HN878 exhibited significant protection in their lungs with BCG doses at 3 × 105—3000 CFU (BALB/c) and 3 × 105—300 CFU (CB6F1). Whereas, a significant protection was seen in both strains of mice with BCG doses at 3 × 105—300 CFU when infected with H37Rv. A significant increase in the frequencies of BCG-specific IFNγ+ IL2+ TNFα+ CD4 T cells in the BCG doses at 3 × 105—3000 CFU (BALB/c) and 3 × 105—300 CFU (CB6F1) was seen. The IFNγ+ IL2+ TNFα+ CD4 T cells correlated with the Mtb burden in the lungs of HN878 infected mice (BALB/c and CB6F1) whereas, IFNγ+ TNFα+ CD4 T cells correlated with the BALB/c mice infected with H37Rv or HN878. The BCG dose at 3000 CFU (an equivalent single human dose in the mice by body weight) is protective in both strains of mice infected with H37Rv or HN878 and may serve an interesting dose to test new TB vaccine in a preclinical animal model.

Modeling Radiation Exposure from Normal Release of 137Cs Radionuclide to Groundwater for Post-Closure Assessment of Serpong Near Surface Disposal Demo Facility

Near-surface disposal (NSD) has been applied in several countries to dispose of low-level radioactive waste. The demo plant of this disposal type is planned to be constructed in Serpong Nuclear Area, Banten. An assessment of radiation exposure is necessary to ensure the safety requirement of the facility in order to support this program. This study aims to estimate radionuclide migration from the proposed NSD demo facility to the environment and the corresponding total human dose using AMBER mathematical modeling. The representative radionuclide,137Cs, was selected because of its high mobility in the environment and the relatively long half-life in the low-level waste inventory. The scenario considered in the modeling was the normal release to the environment through groundwater. Parameters such as initial radionuclide concentration, soil physical parameters of the study site, and disposal design were entered into AMBER software to be calculated using mathematical formulas. The results show that the radionuclide concentration value in the environment is below the safe limit recommended by the Environmental Supervisory Agency. Likewise, the maximum dose received by the community around the facility is 7.40×10-11 mSv/y, 550 years after the post-closure of the facility, which is also below the regulatory limit of 1 mSv/y for the public.