Toxicologic significance of histologic change in the larynx of the rat following inhalation exposure: A critical review

Osimitz, Thomas G.; Droege, Wiebke; Finch, John M.

doi:10.1016/j.taap.2007.08.027

Cited by 33 publications

(25 citation statements)

References 24 publications

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“…The consequences of the lower CD5 expression is consistent with a model of higher TCR signal transduction in T cells from Notch1 ICN-TG mice (Germain, 2002), leading to a potential increase in activation-induced cell death in the periphery. While we were not able to detect any increases in apoptosis in vivo (supplemental figure 3), we and others have previously reported the difficulty in measuring apoptosis in vivo due to rapid clearance by macrophages (Laiosa et al, 2007). Thus we relied on indirect observations, such as splenomegaly to support the hypothesis of increased activation-induced cell death given that spleen enlargement is consistent with the removal of dead and dying cells.…”

Section: Discussioncontrasting

confidence: 65%

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

Ahrenhoerster

Leuthner

Tate

et al. 2015

Toxicology and Applied Pharmacology

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Over half of T-cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch ICN-TG ). Following exposure of adult Notch ICN-TG mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch ICN-TG offspring have a peripheral T-cell pool heavily biased toward the CD4 lineage, while TCDDexposed Notch ICN-TG offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression.

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Section: Discussioncontrasting

confidence: 65%

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

Ahrenhoerster

Leuthner

Tate

et al. 2015

Toxicology and Applied Pharmacology

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“…These minimal and focal changes were regarded to be an adaptive response to the treatment, and no dysfunction of the larynx is to be expected (Kaufmann et al 2009). Those changes are well-known to occur after exposure to irritants and chemicals with unphysiological pH value, like glutaraldehyde, ammonia and dimethylamine (Renne et al 2007;Osimitz et al 2007). Gastroesophageal reflux of the acidic stomach contents, which in Number of animals 3 3 3 3 3 3 3 3 Lung Diffuse histiocytosis (multi-)focal…”

Section: Time (Hours) Compressive Strength (Mpa)mentioning

confidence: 99%

“…It is described that those squamous metaplasia and hyperplasia in the larynx do not progress over time and are partial or complete reversible during recovery periods (Osimitz et al 2007). …”

Section: Time (Hours) Compressive Strength (Mpa)mentioning

confidence: 99%

Nanostructured calcium silicate hydrate seeds accelerate concrete hardening: a combined assessment of benefits and risks

Bräu¹,

Ma‐Hock

Hesse³

et al. 2012

Arch Toxicol

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Nanotechnology creates new possibilities to control and improve material properties for civil infrastructure. Special focus in this area is put on Portland cement and gypsum. Together their annual production is by far larger than for any other material worldwide. Nanomodification of these materials can be done during the few hours between dissolution and hardening, especially by nucleation of the re-crystallization with suitable colloids. Here we report first results in homogeneous seeding of the precipitation of calcium silicate hydrates within a real Portland cement composition. The occupational safety during the production phase and during mixing of concrete paste is addressed in detail by in vivo testing. We perform 5-day inhalation with 21-day recovery in rats and analyze organ-specific toxicity and 71 endpoints from bronchoalveolar lavage (BALF) and blood. In BALF parameters, no test-related changes were observed, indicating the generally low toxicity of the test material. Some mild lesions were observed in larynx level. In the lungs, all animals of the 50 mg/m³ concentration group revealed a minimal to mild increase in alveolar macrophages, which recovered back to control level.

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“…93 Squamous metaplasia represents a common adaptive response to inhaled irritants of diverse types. 98 These changes are not specific to inhaled irritants but also occur as a response to natural respiratory tract pathogens in conventionally housed rats. 99 An international expert group concluded that in the context of inhalation exposure to non-genotoxic chemicals squamous metaplasia in the rodent larynx does not generally represent a pre-neoplastic lesion.…”

Section: Larynx and Tracheamentioning

confidence: 99%

Respiratory Tract

Greaves

2012

Histopathology of Preclinical Toxicity Studies

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Toxicologic significance of histologic change in the larynx of the rat following inhalation exposure: A critical review

Cited by 33 publications

References 24 publications

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

Nanostructured calcium silicate hydrate seeds accelerate concrete hardening: a combined assessment of benefits and risks

Respiratory Tract

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