28d Rat Inhalation Study
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Affymetrix GeneChip Scanner 3000 7G
ORGANISM(S): Rattus norvegicus
SUBMITTER: Sam Ansari
PROVIDER: E-MTAB-1842 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2021-03-18 | E-MTAB-9597 | biostudies-arrayexpress
Project description:Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. This study reports the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Rats were exposed to filtered air (sham), to CHTP1.2 aerosol (at 15, 23 and 50 µg nicotine / L), or to the 3R4F reference cigarette smoke (at 23 µg nicotine / L).
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Project description:Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. This study reports the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Rats were exposed to filtered air (sham), to CHTP1.2 aerosol (at 15, 23 and 50 µg nicotine / L), or to the 3R4F reference cigarette smoke (at 23 µg nicotine / L).
2018-03-19 | PXD008423 | Pride
Project description:Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. This study reports the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Rats were exposed to filtered air (sham), to CHTP1.2 aerosol (at 15, 23 and 50 µg nicotine / L), or to the 3R4F reference cigarette smoke (at 23 µg nicotine / L).
2018-03-19 | PXD008424 | Pride
Project description:A 7-month inhalation study in C57BL/6 mice was conducted to evaluate long-term respiratory toxicity of e-vapor aerosols compared to cigarette smoke and to assess the impact of smoking cessation or switching to an e-vapor product after 3 months of exposure to 3R4F cigarette smoke (CS). In this study, we performed a chronic inhalation (4 h/day, 5 d/week, up to 7 months) study in C57BL/6 mice using a commercial (MarkTen®) e-vapor product and a combustible reference cigarette (3R4F) using a Switching and Cessation study design. A commercial e-vapor product (MarkTen® device [version 2.6.8]; “Test Red”) was supplied by Altria Client Services LLC (Richmond, VA, USA). The Test Red formulation was composed of aerosol formers (propylene glycol [PG] and vegetable glycerol [VG]), ~4% nicotine by weight, and flavors (non-menthol). The 3R4F commercial reference cigarettes were purchased from the University of Kentucky (Lexington, KY). HEPA filtered air at the testing facility (Battelle, West Jefferson, OH) was used as Sham Control. General procedures for animal care and housing met the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) recommendations and requirements stated in the “Guide for Care and Use of Laboratory Animals” [National Research Council (NRC)] and approved by the Institutional Animal Care and Use Committee (IACUC). Female C57BL/6 mice were received from Charles River Kingston (Stone Ridge, NY). Test atmosphere was generated from smoking machines and delivered to the mice through a nose-only exposure system. The modified Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) Reference Method 81 regimen (55/30/5: a 55 ± 0.3 mL puff volume, a puff every 30 seconds, a 5-second puff duration) was used to generate e-vapor aerosol for 130 puffs/cartridge. Mainstream smoke from 3R4F cigarette was generated using a modified Health Canada Intense regimen (55/30/2: a 55 ± 0.3 mL puff volume, a puff every 30 seconds, a 2-second puff duration, and a near-square puff profile) for 8 puffs/cigarette. Female C57BL/6 mice (~10 weeks old) were randomly assigned based on body weight to one of five exposure groups: Sham Control, 3R4F CS, Test Red, Switching, and Cessation. Mice were exposed to 3R4F CS (550 µg/L TPM) or e-vapor aerosols (Test Red; 1100 µg/L TPM) via nose-only inhalation up to 4 h/day, 5 d/week for up to 7 months. After the first 3 months of exposure, groups of 3R4F CS mice were subjected to exposures of: (1) Test Red aerosol (“Switching”) or (2) filtered air (“Cessation”), while a group of mice continued to be exposed to 3R4F CS. Here, the protein expression data for lung tissue assessed by iTRAQ®-based quantitative proteomics is reported.
2021-03-31 | PXD019918 | Pride
Project description:We compared early biological changes in mice after inhalation exposures to cigarette smoke or e-vapor aerosols (MarkTen® cartridge with Carrier, Test-1, or Test-2 formulations; 4% nicotine). Female C57BL/6 mice were exposed to 3R4F cigarette smoke or e-vapor aerosols by nose-only inhalation for up to 4 hours/day, 5 days/week, for 3 weeks. The 3R4F and e-vapor exposures were set to match the target nose port aerosol nicotine concentration (∼41 µg/L). Only the 3R4F group showed postexposure clinical signs such as tremors and lethargy. At necropsy, the 3R4F group had significant increases in lung weight and changes in bronchoalveolar lavage parameters, as well as microscopic findings in the respiratory tract. The e-vapor groups had minimal microscopic changes, including squamous metaplasia in laryngeal epiglottis, and histiocytic infiltrates in the lung (Test-2 group only). The 3R4F group had a higher incidence and severity of microscopic findings compared to any e-vapor group. Transcriptomic analysis also showed that the 3R4F group had the highest number of differentially expressed genes compared to Sham Control. Among e-vapor groups, Test-2 group had more differentially expressed genes but the magnitude of gene expression-based network perturbations in all e-vapor groups was ∼94% less than the 3R4F group. On proteome analysis in the lung, differentially regulated proteins were detected in the 3R4F group only. In conclusion, 3-weeks of 3R4F exposure induced molecular and microscopic changes associated with smoking-related diseases in the respiratory tract, while e-vapor exposures showed substantially reduced biological activities.
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Project description:Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. This study reports the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Rats were exposed to filtered air (sham), to CHTP1.2 aerosol (at 15, 23 and 50 µg nicotine / L), or to the 3R4F reference cigarette smoke (at 23 µg nicotine / L).
2018-04-10 | E-MTAB-6320 | biostudies-arrayexpress
Project description:Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. This study reports the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Rats were exposed to filtered air (sham), to CHTP1.2 aerosol (at 15, 23 and 50 µg nicotine / L), or to the 3R4F reference cigarette smoke (at 23 µg nicotine / L).
2018-04-10 | E-MTAB-6317 | biostudies-arrayexpress
Project description:Modified risk tobacco products (MRTPs) have the potential to reduce smoking-related health risks. The Carbon Heated Tobacco Product 1.2 (CHTP1.2) is a potential MRTP that uses a pressed carbon heat source to generate an aerosol by heating tobacco. This study reports the results from the systems toxicology arm of a 90-day rat inhalation study (OECD test guideline 413) to assess the effects of CHTP1.2 aerosol compared with cigarette smoke (CS). Rats were exposed to filtered air (sham), to CHTP1.2 aerosol (at 15, 23 and 50 µg nicotine / L), or to the 3R4F reference cigarette smoke (at 23 µg nicotine / L).
2018-04-10 | E-MTAB-6319 | biostudies-arrayexpress
Project description:The objective of the study was to characterize the toxicity due to sub-chronic inhalation of test atmospheres from the heat not burn modified risk tobacco product (MRTP) - Tobacco Heating System version 2.2 (THS2.2) and to compare it to the toxicity inherent to the inhalation of mainstream smoke (MS) from the Reference Cigarette 3R4F (University_of_Kentucky, 2003). The 90-day nose-only inhalation study on Sprague-Dawley rats was performed according to the Organization for Economic Co-operation and Development (OECD) Test Guideline 413 (OECD, 2009), with special emphasis on histopathology of the respiratory tract, lung inflammation and additional systems toxicology-based assessment using transcriptomics. Animals were exposed to mainstream smoke from 3R4F reference cigarettes or THS2.2 mainstream aerosol at 3 target nicotine concentrations. The exposure regimen consisted of 6 hours a day, 5 days per week for 13 weeks, followed by 42 days recovery period. Exposure-related changes such as increased blood neutrophil count, decreased blood lymphocyte count, increased activity of alkaline phosphatase in serum and decreased cholesterol and glucose in serum were observed in 3R4F and THS2.2 exposed animals. Reduction in respiratory minute volume was significantly less pronounced in THS2.2 as compared to 3R4F-exposed groups. Histopathological findings in the respiratory tract including epithelial cell hyperplasia, squamous metaplasia, atrophy and accumulation of pigmented alveolar macrophages were significantly lower in THS2.2 than in 3R4F exposed groups. The degree of lung inflammation as indicated by accumulation of immune cells and pro-inflammatory and chemotactic cytokines in bronchioalveolar lavage fluid were significantly lower in THS2.2 as compared to 3R4F exposed groups. Transcriptomics data obtained from nasal epithelium and lung parenchyma showed concentration-dependent gene expression changes following 3R4F exposure that were much less pronounced in the THS2.2-exposed groups. In summary, the data indicates that the aerosol from THS2.2 did not cause additional toxicity as compared to the smoke from the 3R4F conventional cigarette. The toxicity on respiratory tract organs in THS2.2 exposed animals was much lower than in the rats exposed to 3R4F reference cigarette. Overall, the changes observed following exposure to THS2.2 can be considered mild and are very similar to previously published effects caused by nicotine only exposure at similar test atmosphere concentrations.
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