scholarly journals Reduced Chronic Toxicity and Carcinogenicity in A/J Mice in Response to Life-Time Exposure to Aerosol From a Heated Tobacco Product Compared With Cigarette Smoke

2020 ◽  
Vol 178 (1) ◽  
pp. 44-70
Author(s):  
Ee Tsin Wong ◽  
Karsta Luettich ◽  
Subash Krishnan ◽  
Sin Kei Wong ◽  
Wei Ting Lim ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Chronic Toxicity ◽  
Tumor Development ◽  
Life Time ◽  
Heating System ◽  
Heart Weight ◽  
Spleen Weight ◽  
Weight Changes ◽  
Inhalation Study ◽  
Lower Survival Rate

Abstract We conducted an inhalation study, in accordance with Organisation for Economic Co-operation and Development Test Guideline 453, exposing A/J mice to tobacco heating system (THS) 2.2 aerosol or 3R4F reference cigarette smoke (CS) for up to 18 months to evaluate chronic toxicity and carcinogenicity. All exposed mice showed lower thymus and spleen weight, blood lymphocyte counts, and serum lipid concentrations than sham mice, most likely because of stress and/or nicotine effects. Unlike THS 2.2 aerosol-exposed mice, CS-exposed mice showed increased heart weight, changes in red blood cell profiles and serum liver function parameters. Similarly, increased pulmonary inflammation, altered lung function, and emphysematous changes were observed only in CS-exposed mice. Histopathological changes in other respiratory tract organs were significantly lower in the THS 2.2 aerosol-exposed groups than in the CS-exposed group. Chronic exposure to THS 2.2 aerosol also did not increase the incidence or multiplicity of bronchioloalveolar adenomas or carcinomas relative to sham, whereas CS exposure did. Male THS 2.2 aerosol-exposed mice had a lower survival rate than sham mice, related to an increased incidence of urogenital issues that appears to be related to congenital factors rather than test item exposure. The lower impact of THS 2.2 aerosol exposure on tumor development and chronic toxicity is consistent with the significantly reduced levels of harmful and potentially harmful constituents in THS 2.2 aerosol relative to CS. The totality of the evidence from this study further supports the risk reduction potential of THS 2.2 for lung diseases in comparison with cigarettes.

Exposure to cigarette smoke and aerosol from the potential reduced risk product THS2.2 on A/J mice in life-time inhalation study

2017 ◽  
Vol 280 ◽  
pp. S143
Author(s):  
Emilija Veljkovic ◽  
Ee Tsin Wong ◽  
Karsta Luettich ◽  
Emmanuel Guedj ◽  
Remi Dulize ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Life Time ◽  
Inhalation Study ◽  
Reduced Risk

scholarly journals A 7-month inhalation toxicology study in C57BL/6 mice demonstrates reduced pulmonary inflammation and emphysematous changes following smoking cessation or switching to e-vapor products

2021 ◽  
Vol 5 ◽  
pp. 239784732199587
Author(s):  
Ashutosh Kumar ◽  
Ulrike Kogel ◽  
Marja Talikka ◽  
Celine Merg ◽  
Emmanuel Guedj ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cigarette Smoke ◽  
Pulmonary Inflammation ◽  
Clinical Signs ◽  
Inhalation Study ◽  
Toxicology Study ◽  
Nasal Tissue ◽  
Product Switching ◽  
The Impact

Cigarette smoking causes serious diseases, including lung cancer, atherosclerotic coronary artery disease, peripheral vascular disease, chronic bronchitis, and emphysema. While cessation remains the most effective approach to minimize smoking-related disease, alternative non-combustible tobacco-derived nicotine-containing products may reduce disease risks among those unable or unwilling to quit. E-vapor aerosols typically contain significantly lower levels of smoke-related harmful and potentially harmful constituents; however, health risks of long-term inhalation exposures are unknown. We designed a 7-month inhalation study in C57BL/6 mice to evaluate long-term respiratory toxicity of e-vapor aerosols compared to cigarette smoke and to assess the impact of smoking cessation (Cessation group) or switching to an e-vapor product (Switching group) after 3 months of exposure to 3R4F cigarette smoke (CS). There were no significant changes in in-life observations (body weights, clinical signs) in e-vapor groups compared to the Sham Control. The 3R4F CS group showed reduced respiratory function during exposure and had lower body weight and showed transient signs of distress post-exposure. Following 7 months of exposure, e-vapor aerosols resulted in no or minimal increase in pulmonary inflammation, while exposure to 3R4F CS led to impairment of lung function and caused marked lung inflammation and emphysematous changes. Biological changes observed in the Switching group were similar to the Cessation group. 3R4F CS exposure dysregulated the lung and nasal tissue transcriptome, while these molecular effects were substantially lower in the e-vapor group. Results from this study demonstrate that in comparison with 3R4F CS, e-vapor aerosols induce substantially lower biological responses including pulmonary inflammation and emphysematous changes, and that complete switching from CS to e-vapor products significantly reduces biological changes associated with CS in C57BL/6 mice.

Robustness of HPHC Reduction in THS 2.2 Aerosol Relative to 3R4F Reference Cigarette Smoke under Extreme Climatic Conditions

2021 ◽  
Vol 30 (3) ◽  
pp. 109-126
Author(s):  
Laurent Poget ◽  
Catherine Goujon ◽  
Samuel Kleinhans ◽  
Serge Maeder ◽  
Jean-Pierre Schaller
Keyword(s):  
Cigarette Smoke ◽  
Heating System ◽  
Tobacco Product ◽  
Climatic Conditions ◽  
Mainstream Smoke ◽  
Humid Climate ◽  
Experimental Conditions ◽  
Puff Volume ◽  
Temperature And Humidity ◽  
Health Canada

Summary In order to assess robustness for the reduction of harmful and potentially harmful constituent (HPHC) levels generated by the Tobacco Heating System 2.2 (THS 2.2), a heated tobacco product, we compared the aerosol of this product with mainstream smoke from the 3R4F reference cigarette under different conditions of temperature and humidity. The desired climatic conditions were achieved by using an air-conditioning system coupled with the smoking-machine housing. Two extreme climatic conditions were selected, representing a “Hot and Dry” climate (30 °C and 35% relative humidity RH) and a “Hot and Very Humid” climate (30 °C and 75% RH). In addition, aerosol and smoke were generated using the standard conditions recognized for smoking-machine analyses of tobacco products (22 °C and 60% RH), which were close to the climatic conditions defined for “Subtropical and Mediterranean” environments (25 °C and 60% RH). The experimental conditions were chosen to simulate the use of THS 2.2 and cigarettes under extreme conditions of temperature and humidity. HeatSticks and cigarettes taken from freshly opened packs were subjected to short-term conditioning from two to a few more days under the same experimental conditions. We analyzed 54 HPHCs in THS 2.2 aerosol and 3R4F cigarette smoke, generated in accordance with the Health Canada Intense (HCI) standard, using modified temperature and humidity conditions for sample conditioning and machine-smoking experiments. We used a volume-adjusted approach for comparing HPHC reductions across the different climatic conditions investigated. Although a single puffing regimen was used, the total puff volume recorded for the 3R4F cigarette smoke varied due to the influence of temperature and humidity on combustion rate, which justified the use of a volume-adjusted approach. Volume-adjusted yields were derived from HPHC yields expressed in mass-per-tobacco stick normalized per total puff volume. The results indicated that, regardless of the considered climatic conditions, the HPHC levels investigated in THS 2.2 aerosol were reduced by at least 90%, on average, when compared with the concentrations in 3R4F cigarette mainstream smoke. This confirmed the robustness in performance for THS 2.2 to deliver reduced levels of HPHCs under the extreme climatic conditions investigated in this study. In order to further characterize the robustness of these reductions, the lowest reduction performance achieved for individual HPHCs across all climatic conditions was used to define the threshold for a robust reduction. The majority of the 54 HPHCs investigated in THS 2.2 aerosol showed more than 90% reduction. Calculations derived from nicotine-adjusted yields also confirmed robust reductions for all investigated HPHCs. The small differences in absolute reduction between the volume- and nicotine-adjusted approaches were predominantly attributed to a combination of the differences in both nominal nicotine deliveries and total puff volumes between THS 2.2 and 3R4F cigarettes; however, this did not influence the determination of robustness. Our findings confirm the value of this approach for assessing the robustness of a product’s performance under different climatic conditions.

Cigarette smoke inhalation study for lung tumorigenicity in A/J mice

2010 ◽  
Vol 01 (01) ◽  
Author(s):  
R. B. Lichtner ◽  
B. Friedrichs ◽  
A. Buettner ◽  
F. Van Overveld ◽  
W. Stinn
Keyword(s):  
Cigarette Smoke ◽  
Smoke Inhalation ◽  
Inhalation Study

Chronische Pankreatitis und Pankreaskarzinom – Tumorrisiko und Screening

2018 ◽  
Vol 143 (12) ◽  
pp. 895-906 ◽  
Author(s):  
Georg Beyer ◽  
Jan D’Haese ◽  
Steffen Ormanns ◽  
Julia Mayerle
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Clinical Laboratory ◽  
Chronische Pankreatitis ◽  
Tumor Development ◽  
Life Time ◽  
High Morbidity ◽  
Patients At Risk ◽  
Nicotine Consumption

AbstractChronic pancreatitis is a fibroinflammatory syndrome of the exocrine pancreas, which is characterized by an increasing incidence, high morbidity and lethality. Common etiologies besides alcohol and nicotine consumption include genetic causes and risk factors. The life time risk for the development of pancreatic cancer is elevated 13- to 45-fold depending on the underlying etiology. In patients with chronic pancreatitis clinical, laboratory and imaging surveillance for early detection of complications, including pancreatic cancer, is recommended, although the available methods lack the desired sensitivity and specificity. In this article we review the epidemiology, etiologies and risk factors for chronic pancreatitis and pancreatic cancer and discuss current recommendations for screening and management of patients at risk for tumor development.

scholarly journals Genome-wide association study identifies loci and candidate genes for internal organ weights in Simmental beef cattle

2018 ◽  
Vol 50 (7) ◽  
pp. 523-531 ◽  
Author(s):  
Bingxing An ◽  
Jiangwei Xia ◽  
Tianpeng Chang ◽  
Xiaoqiao Wang ◽  
Jian Miao ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Snp Array ◽  
Genome Wide Association ◽  
Heart Weight ◽  
Spleen Weight ◽  
Internal Organs ◽  
Genome Wide ◽  
A Genome

Cattle internal organs as accessible raw materials have a long history of being widely used in beef processing, feed and pharmaceutical industry. These traits not only are of economic interest to breeders, but they are intrinsically linked to many valuable traits, such as growth, health, and productivity. Using the Illumina Bovine HD 770K SNP array, we performed a genome-wide association study for heart weight, liver weight, spleen weight, lung weight, and kidney weight in 1,217 Simmental cattle. In our research, 38 significant single nucleotide polymorphisms (SNPs) ( P < 1.49 × 10−6) were identified for five internal organ weight traits. These SNPs are within or near 13 genes, and some of them have been reported previously, including NDUFAF4, LCORL, BT.94996, SLIT2, FAM184B, LAP3, BBS12, MECOM, CD300LF, HSD17B3, TLR4, MXI1, and MB21D2. In addition, we detected four haplotype blocks on BTA6 containing 18 significant SNPs associated with spleen weight. Our results offer worthy insights into understanding the genetic mechanisms of internal organs' development, with potential application in breeding programs of Simmental beef cattle.

scholarly journals Physical activity, body fat and experimental cardiac necrosis

1970 ◽  
Vol 24 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Jana Pařézkov´ ◽  
Eva Faltov´
Keyword(s):  
Physical Activity ◽  
Body Fat ◽  
Heart Weight ◽  
Control Group ◽  
Age Group ◽  
Weight Changes ◽  
Cardiac Damage ◽  
Percentage Body Fat ◽  
Exercise Regime ◽  
Cardiac Necrosis

1. The effects of varying levels of physical activity were tested in rats, starting at ages of 21, 32 and 55 days and continuing until go, 100, 125 and 205 days.2. Weight changes did not differ significantly between the exercise groups, except in the groups tested up to 205 days, when both the exercised group and the group with limited activity were significantly lighter than the control group.3. The weight of the soleus muscle was significantly greater in the exercised rats compared with controls and rats with limited activity, except in the oldest age-group. The weight of the tibialis anticus muscle did not differ significantly between the different exercise regimes.4. Heart weight was not significantly affected by the exercise regime, except that in rats studied from 55 to 125 days; the group with limited activity had significantly lighter hearts than those in the control group or the exercised group.5. The percentage body fat was lower in the exercised group compared with the limited activity group, and was less than the control group in both the rats studied up to 205 days and those studied from 21 to 90 days.6. Isoprenaline produced less cardiac damage in the exercised rats than in controls or in rats with limited activity. Animals who died following injection of isoprenaline had a higher percentage body fat than those animals with minimal cardiac damage.

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