Project description:Carbon black nanoparticles (CBNP) are the most widely produced nanomaterial and are thus a concern for occupational exposures. CBNPs are known to cause inflammation upon inhalation; however, detailed time course data to evaluate the changing nature of inflammatory responses have not been evaluated. In this study, we investigate the short- and longer-term effects of CBNP following a single intratracheal exposure. Female C57BL/6BomTac mice were exposed to CBNPs (printex 90) via a single intratracheal instillation of 162 µg/mouse alongside vehicle controls. Mice were examined 3 hours (hrs), and 1, 2, 3, 4, 5, 14, and 42 days (d) post-exposure. Global gene expression was assessed using DNA microarrays in parallel with analysis of pulmonary inflammation assessed as bronchoalveolar lavage (BAL) cell counts and DNA strand breaks assessed by the comet assay. Pulmonary inflammation in terms of increased neutrophil influx was obverved at all time points. Increased levels of DNA strand breaks were observed in BAL cells 3 hrs post exposure and in lung tissue 2-5 d post exposure. Approximately 2600 significant differentially expressed genes (±1.5 fold; p ≤0.05) across all of the time-points in the lungs of exposed mice were identified upon comparison to time-matched controls. Transcriptional alterations were enriched for genes involved in common respiratory infectious diseases. The perturbed biological processes and pathways were primarily related to immune-inflammatory responses and acute phase responses, consistent with the BAL inflammatory profiles. Gene and pathway analysis revealed a biphasic inflammatory response, with changes occurring as early as 3 hrs post-exposure and declining to base-levels by 3 d post-exposure, but with inflammatory pathways increasing in response again at 14 d and persisting to 42 d post-exposure. Other perturbed pathways included DNA repair and apoptosis, cell cycle regulation, and muscle contraction. Single CBNP exposure induced a biphasic inflammatory response that lasted until 42 d post-exposure. Such persistent inflammatory response raises concerns over the chronic effects of CBNP exposure since the administered dose corresponds to pulmonary deposition in mice during nine 8-hour working days at the current occupational exposure limit for carbon black.

Project description:BackgroundThe toxicokinetic behaviour of nanostructured particles following pulmonary or oral deposition is of great scientific interest. In this toxicokinetic study, following the general principles of OECD TG 417, the systemic availability of carbon black, a nanostructured material consisting of agglomerated aggregates was characterised.MethodsEach of two grades of beryllium-7 labelled carbon black (Monarch® 1000, oxidized and Printex® 90; untreated) was administered either intratracheally or orally to adult rats. Independent of route, rats received a single dose of approximately 0.3 mg radiolabelled carbon black. A total of 12 rats were treated per grade and per exposure route: 4 females each for feces/urine/organs and serial blood kinetics; 4 males for organs. At necropsy, the complete suite of organs was analysed for females, but only the lungs, liver, kidney, reproductive organs for males.ResultsIn the pulmonarily exposed animals, 7Be-Monarch® 1000 and 7Be-Printex® 90 was detected in feces in the first 3 days after treatment at significant levels, i.e. 17.6% and 8.2%, respectively. In urine, small percentages of 6.7% and 0.4% were observed, respectively. In blood, radioactivity, representative of carbon black was within the background noise of the measurement method. At necropsy, 20 days post-instillation, both test items were practically exclusively found in lungs (75.1% and 91.0%, respectively) and in very small amounts (approximately 0.5%) in the lung-associated lymph nodes (LALN). In the other organs/tissues the test item was not detectable. BAL analyses indicated that carbon black particles were completely engulfed by alveolar macrophages. In orally exposed animals, 98% (7Be-Monarch® 1000) and 99% (7Be-Printex® 90) of the measured radioactivity was detected in feces. Excretion was complete within the first 3 days following treatment. 1.3% and 0.5% of measured activity was attributable to urine in animals that received 7Be-Monarch® 1000 and 7Be-Printex® 90, respectively. Radioactivity was absent in blood and other organs and tissues.ConclusionRadioactivity, representative of carbon black, was not detected beyond the experimentally defined limit of quantitation systemically after deposition in lungs or stomach in rats. Under these experimental conditions, the two CB samples were not shown to translocate beyond the lung or the GI tract into the blood compartment.

Project description:Exposure to nanomaterials (NM) during sensitive stages of development may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM-induced stress, such as inflammation during gestation, can lead to secondary effects in the growing fetus. Time mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Milli Q water) or one of three concentrations (2.75, 13.5 or 67 µg/animal) of carbon black Printex 90 (CB) dispersions on gestational days 7, 10, 15 and 18 to a total final dose of 11, 54 or 268 µg/animal. Male and female newborns were sacrificed on day 2 after birth (PND2, 4 days after the last maternal exposure) and dams were sacrificed after weaning of offspring (26-27 days post-exposure). Histopathology, DNA microarrays, pathway-specific RT-PCR arrays, focussed RT-PCR, and tissue protein analysis were employed to characterize pulmonary response in dams exposed to CB during gestation. Gene expression profiles in newborn livers were interpreted in light of toxic effects of CB to dams indicated by gene expression profiles of dam lungs. Although retention of CB particles was observed in dams from both medium and high dose groups, neutrophil-marked inflammation was significant only in the high dose group dams. Inflammation in dams was accompanied by altered expression of several cytokines and chemokines both at the transcriptional and tissue protein levels. Analysis of newborn livers by DNA microarrays revealed that female offspring were much more sensitive to maternal stress than males. Cellular signalling, inflammation, immune response, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males however, responded with subtle changes in genes involved in metabolism. At present, the implications of altered biological pathways in offspring in response to in utero exposure to particles are not well understood. Further investigation will be required to determine if there are long term consequences to offspring in terms of health and responses to environmental stresses. This SuperSeries is composed of the SubSeries listed below.

Project description:Exposure to nanomaterials (NM) during sensitive stages of development may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM-induced stress, such as inflammation during gestation, can lead to secondary effects in the growing fetus. Time mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Milli Q water) or one of three concentrations (2.75, 13.5 or 67 µg/animal) of carbon black Printex 90 (CB) dispersions on gestational days 7, 10, 15 and 18 to a total final dose of 11, 54 or 268 µg/animal. Male and female newborns were sacrificed on day 2 after birth (PND2, 4 days after the last maternal exposure) and dams were sacrificed after weaning of offspring (26-27 days post-exposure). Histopathology, DNA microarrays, pathway-specific RT-PCR arrays, focussed RT-PCR, and tissue protein analysis were employed to characterize pulmonary response in dams exposed to CB during gestation. Gene expression profiles in newborn livers were interpreted in light of toxic effects of CB to dams indicated by gene expression profiles of dam lungs. Although retention of CB particles was observed in dams from both medium and high dose groups, neutrophil-marked inflammation was significant only in the high dose group dams. Inflammation in dams was accompanied by altered expression of several cytokines and chemokines both at the transcriptional and tissue protein levels. Analysis of newborn livers by DNA microarrays revealed that female offspring were much more sensitive to maternal stress than males. Cellular signalling, inflammation, immune response, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males however, responded with subtle changes in genes involved in metabolism. At present, the implications of altered biological pathways in offspring in response to in utero exposure to particles are not well understood. Further investigation will be required to determine if there are long term consequences to offspring in terms of health and responses to environmental stresses.

Dataset Information

Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation.

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Carbon black nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 mice following a single intratracheal instillation.

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