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Article ; Online: Distribution of 2,2',5,5'-Tetrachlorobiphenyl (PCB52) Metabolites in Adolescent Rats after Acute Nose-Only Inhalation Exposure.

Bullert, Amanda J / Li, Xueshu / Gautam, Binita / Wang, Hui / Adamcakova-Dodd, Andrea / Wang, Kai / Thorne, Peter S / Lehmler, Hans-Joachim

Environmental science & technology

2024 Volume 58, Issue 14, Page(s) 6105–6116

Abstract: Inhalation of PCB-contaminated air is increasingly recognized as a route for PCB exposure. Because limited information about the disposition of PCBs following inhalation exposure is available, this study investigated the disposition of 2,2',5,5'- ... ...

Abstract	Inhalation of PCB-contaminated air is increasingly recognized as a route for PCB exposure. Because limited information about the disposition of PCBs following inhalation exposure is available, this study investigated the disposition of 2,2',5,5'-tetrachlorobiphenyl (PCB52) and its metabolites in rats following acute, nose-only inhalation of PCB52. Male and female Sprague-Dawley rats (50-58 days of age, 210 ± 27 g; n = 6) were exposed for 4 h by inhalation to approximately 14 or 23 μg/kg body weight of PCB52 using a nose-only exposure system. Sham animals (n = 6) were exposed to filtered lab air. Based on gas chromatography-tandem mass spectrometry (GC-MS/MS), PCB52 was present in adipose, brain, intestinal content, lung, liver, and serum. 2,2',5,5'-Tetrachlorobiphenyl-4-ol (4-OH-PCB52) and one unknown monohydroxylated metabolite were detected in these compartments except for the brain. Liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis identified several metabolites, including sulfated, methoxylated, and dechlorinated PCB52 metabolites. These metabolites were primarily found in the liver (7 metabolites), lung (9 metabolites), and serum (9 metabolites) due to the short exposure time. These results demonstrate for the first time that complex mixtures of sulfated, methoxylated, and dechlorinated PCB52 metabolites are formed in adolescent rats following PCB52 inhalation, laying the groundwork for future animal studies of the adverse effects of inhaled PCB52.
MeSH term(s)	Rats ; Male ; Female ; Animals ; Inhalation Exposure/analysis ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Polychlorinated Biphenyls/analysis ; Polychlorinated Biphenyls/metabolism
Chemical Substances	2,5,2',5'-tetrachlorobiphenyl (1EH557950R) ; Polychlorinated Biphenyls (DFC2HB4I0K)
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.3c09527
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Article: Toxicity Assessment of 91-Day Repeated Inhalation Exposure to an Indoor School Air Mixture of PCBs

Wang, Hui / Adamcakova-Dodd, Andrea / Lehmler, Hans-Joachim / Hornbuckle, Keri C. / Thorne, Peter S.

Environmental science & technology. 2022 Jan. 07, v. 56, no. 3

2022

Abstract: School indoor air contaminated with polychlorinated biphenyls (PCBs) released from older building materials and paint pigments may pose health risks to children, as well as teachers and staff, by inhalation of PCBs. The health effects of long-term ... ...

Abstract	School indoor air contaminated with polychlorinated biphenyls (PCBs) released from older building materials and paint pigments may pose health risks to children, as well as teachers and staff, by inhalation of PCBs. The health effects of long-term inhalation exposure to PCBs are poorly understood. We conducted a comprehensive toxicity assessment of 91-day repeated inhalation exposure to a lab-generated mixture of PCBs designed to emulate indoor school air, combining transcriptomics, metabolomics, and neurobehavioral outcomes. Female Sprague–Dawley rats were exposed to school air mixture (SAM+) at a concentration of 45.5 ± 5.9 μg/m³ ∑₂₀₉PCB or filtered air 4 h/day, 6 days/week for 13 weeks using nose-only exposure systems. The congener-specific PCB body burden was quantified in major tissues using GC-MS/MS. The generated SAM+ vapor recapitulated the target school air profile with a similarity coefficient, cos θ of 0.91. PCB inhalation yielded 875–9930 ng/g ∑₂₀₉PCBₗᵢₚᵢd wₑᵢgₕₜ levels in tissues in the following ascending order: brain < liver < lung < serum < adipose tissue. We observed that PCB exposure impaired memory, induced anxiety-like behavior, significantly reduced white blood cell counts, mildly disrupted metabolomics in plasma, and influenced transcription processes in the brain with 274 upregulated and 58 downregulated genes. With relatively high exposure and tissue loading, evidence of toxicity from half the end points tested was seen in the rats.
Keywords	adipose tissue ; air ; blood serum ; brain ; breathing ; environmental science ; females ; inhalation exposure ; liver ; lungs ; memory ; metabolomics ; polychlorinated biphenyls ; toxicity ; transcriptomics ; vapors
Language	English
Dates of publication	2022-0107
Size	p. 1780-1790.
Publishing place	American Chemical Society
Document type	Article
ISSN	1520-5851
DOI	10.1021/acs.est.1c05084
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Article: Validation of blood arsenic and manganese assessment from archived clotted erythrocyte fraction in an urban cohort of mother-child dyads

Haque, Ezazul / Moran, Margaret E. / Wang, Hui / Adamcakova-Dodd, Andrea / Thorne, Peter S.

Science of the total environment. 2022 Mar. 01, v. 810

2022

Abstract: Exposure to arsenic (As) and manganese (Mn) from contaminated food, drinking water and dust are linked to a host of adverse health effects. The recent discovery of unmonitored community exposures to hazardous levels of metals, as seen in the Flint Water ... ...

Abstract	Exposure to arsenic (As) and manganese (Mn) from contaminated food, drinking water and dust are linked to a host of adverse health effects. The recent discovery of unmonitored community exposures to hazardous levels of metals, as seen in the Flint Water Crisis and East Chicago, have demonstrated a need for novel biomonitoring methods utilizing samples other than whole blood. Here, we present a method utilizing clotted erythrocyte fraction samples, a blood component commonly archived in biorepositories, to predict whole blood levels of As and Mn. This method would allow for innovative retrospective assessments of environmental exposures in previously unused samples. Whole blood and clotted erythrocyte fraction samples were simultaneously collected from 84 participants in the Airborne Exposure to Semivolatile Organic Pollutants (AESOP) cohort study of mother-child dyads in East Chicago. Clotted erythrocyte fraction samples were prepared by alkaline dilution and subsequently analyzed using inductively coupled plasma-mass spectrometry. A strong linear relationship was observed between whole blood and clotted erythrocyte fraction with Pearson correlation coefficients (r, p < 0.001) of 0.74, and 0.82 for As and Mn, respectively. Modeled whole blood Mn levels predicted from clotted erythrocyte fractions evaluated at a test threshold representing the NHANES median of 9.7 μg/L, were found to have diagnostic sensitivity of 88% and specificity of 71%. Clotted erythrocyte partitioning of As was tested on a wide range of oral gavage doses using a rat model. Results from this investigation demonstrate clotted erythrocyte fraction samples are a viable alternative biological sample for retrospective public health surveillance of environmental exposure to As and Mn.
Keywords	National Health and Nutrition Examination Survey ; animal models ; arsenic ; cohort studies ; diagnostic sensitivity ; dust ; environment ; environmental exposure ; environmental monitoring ; erythrocytes ; food contamination ; manganese ; public health ; volatile organic compounds
Language	English
Dates of publication	2022-0301
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2021.152320
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Article ; Online: Toxicity Assessment of 91-Day Repeated Inhalation Exposure to an Indoor School Air Mixture of PCBs.

Wang, Hui / Adamcakova-Dodd, Andrea / Lehmler, Hans-Joachim / Hornbuckle, Keri C / Thorne, Peter S

Environmental science & technology

2022 Volume 56, Issue 3, Page(s) 1780–1790

Abstract	School indoor air contaminated with polychlorinated biphenyls (PCBs) released from older building materials and paint pigments may pose health risks to children, as well as teachers and staff, by inhalation of PCBs. The health effects of long-term inhalation exposure to PCBs are poorly understood. We conducted a comprehensive toxicity assessment of 91-day repeated inhalation exposure to a lab-generated mixture of PCBs designed to emulate indoor school air, combining transcriptomics, metabolomics, and neurobehavioral outcomes. Female Sprague-Dawley rats were exposed to school air mixture (SAM+) at a concentration of 45.5 ± 5.9 μg/m
MeSH term(s)	Air Pollution, Indoor ; Animals ; Female ; Inhalation Exposure/analysis ; Polychlorinated Biphenyls/analysis ; Polychlorinated Biphenyls/toxicity ; Rats ; Rats, Sprague-Dawley ; Schools ; Tandem Mass Spectrometry
Chemical Substances	Polychlorinated Biphenyls (DFC2HB4I0K)
Language	English
Publishing date	2022-01-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.1c05084
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Article ; Online: Cerium Oxide Enhances the Toxicity of Zinc Oxide Nanoparticles in Human Lung Epithelial Cell Cultures.

Al Rashaideh, Tasnim / Metwali, Nervana / Perry, Sarah S / Adamcakova-Dodd, Andrea / Thorne, Peter S

Toxics

2022 Volume 10, Issue 9

Abstract: Recently, many approaches have been developed to improve the performance of nanomaterials. Combining more than one nanomaterial is one such approach that achieves superior results. However, during the fabrication of nanomaterials or formulation of end ... ...

Abstract	Recently, many approaches have been developed to improve the performance of nanomaterials. Combining more than one nanomaterial is one such approach that achieves superior results. However, during the fabrication of nanomaterials or formulation of end products, materials can be released into the ambient air and be inhaled by workers. The adverse health outcomes of inhaling such compounds are unknown. In this study, we examined such effects in combining two of the most utilized nanomaterials in several industrial sectors: zinc oxide (ZnO) and cerium oxide (CeO
Language	English
Publishing date	2022-09-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2733883-6
ISSN	2305-6304 ; 2305-6304
ISSN (online)	2305-6304
ISSN	2305-6304
DOI	10.3390/toxics10090522
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Article ; Online: Validation of blood arsenic and manganese assessment from archived clotted erythrocyte fraction in an urban cohort of mother-child dyads.

Haque, Ezazul / Moran, Margaret E / Wang, Hui / Adamcakova-Dodd, Andrea / Thorne, Peter S

The Science of the total environment

2021 Volume 810, Page(s) 152320

Abstract	Exposure to arsenic (As) and manganese (Mn) from contaminated food, drinking water and dust are linked to a host of adverse health effects. The recent discovery of unmonitored community exposures to hazardous levels of metals, as seen in the Flint Water Crisis and East Chicago, have demonstrated a need for novel biomonitoring methods utilizing samples other than whole blood. Here, we present a method utilizing clotted erythrocyte fraction samples, a blood component commonly archived in biorepositories, to predict whole blood levels of As and Mn. This method would allow for innovative retrospective assessments of environmental exposures in previously unused samples. Whole blood and clotted erythrocyte fraction samples were simultaneously collected from 84 participants in the Airborne Exposure to Semivolatile Organic Pollutants (AESOP) cohort study of mother-child dyads in East Chicago. Clotted erythrocyte fraction samples were prepared by alkaline dilution and subsequently analyzed using inductively coupled plasma-mass spectrometry. A strong linear relationship was observed between whole blood and clotted erythrocyte fraction with Pearson correlation coefficients (r, p < 0.001) of 0.74, and 0.82 for As and Mn, respectively. Modeled whole blood Mn levels predicted from clotted erythrocyte fractions evaluated at a test threshold representing the NHANES median of 9.7 μg/L, were found to have diagnostic sensitivity of 88% and specificity of 71%. Clotted erythrocyte partitioning of As was tested on a wide range of oral gavage doses using a rat model. Results from this investigation demonstrate clotted erythrocyte fraction samples are a viable alternative biological sample for retrospective public health surveillance of environmental exposure to As and Mn.
MeSH term(s)	Animals ; Arsenic ; Cohort Studies ; Environmental Exposure/analysis ; Erythrocytes ; Manganese ; Mother-Child Relations ; Nutrition Surveys ; Rats ; Retrospective Studies
Chemical Substances	Manganese (42Z2K6ZL8P) ; Arsenic (N712M78A8G)
Language	English
Publishing date	2021-12-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2021.152320
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Article ; Online: Time course of pulmonary inflammation and trace element biodistribution during and after sub-acute inhalation exposure to copper oxide nanoparticles in a murine model.

Areecheewakul, Sudartip / Adamcakova-Dodd, Andrea / Haque, Ezazul / Jing, Xuefang / Meyerholz, David K / O'Shaughnessy, Patrick T / Thorne, Peter S / Salem, Aliasger K

Particle and fibre toxicology

2022 Volume 19, Issue 1, Page(s) 40

Abstract: Background: It has been shown that copper oxide nanoparticles (CuO NPs) induce pulmonary toxicity after acute or sub-acute inhalation exposures. However, little is known about the biodistribution and elimination kinetics of inhaled CuO NPs from the ... ...

Abstract	Background: It has been shown that copper oxide nanoparticles (CuO NPs) induce pulmonary toxicity after acute or sub-acute inhalation exposures. However, little is known about the biodistribution and elimination kinetics of inhaled CuO NPs from the respiratory tract. The purposes of this study were to observe the kinetics of pulmonary inflammation during and after CuO NP sub-acute inhalation exposure and to investigate copper (Cu) biodistribution and clearance rate from the exposure site and homeostasis of selected trace elements in secondary organs of BALB/c mice. Results: Sub-acute inhalation exposure to CuO NPs led to pulmonary inflammation represented by increases in lactate dehydrogenase, total cell counts, neutrophils, macrophages, inflammatory cytokines, iron levels in bronchoalveolar lavage (BAL) fluid, and lung weight changes. Dosimetry analysis in lung tissues and BAL fluid showed Cu concentration increased steadily during exposure and gradually declined after exposure. Cu elimination from the lung showed first-order kinetics with a half-life of 6.5 days. Total Cu levels were significantly increased in whole blood and heart indicating that inhaled Cu could be translocated into the bloodstream and heart tissue, and potentially have adverse effects on the kidneys and spleen as there were significant changes in the weights of these organs; increase in the kidneys and decrease in the spleen. Furthermore, concentrations of selenium in kidneys and iron in spleen were decreased, pointing to disruption of trace element homeostasis. Conclusions: Sub-acute inhalation exposure of CuO NPs induced pulmonary inflammation, which was correlated to Cu concentrations in the lungs and started to resolve once exposure ended. Dosimetry analysis showed that Cu in the lungs was translocated into the bloodstream and heart tissue. Secondary organs affected by CuO NPs exposure were kidneys and spleen as they showed the disruption of trace element homeostasis and organ weight changes.
MeSH term(s)	Animals ; Copper/toxicity ; Disease Models, Animal ; Inhalation Exposure/adverse effects ; Iron ; Metal Nanoparticles/toxicity ; Mice ; Mice, Inbred BALB C ; Nanoparticles/toxicity ; Oxides ; Pneumonia ; Tissue Distribution ; Trace Elements
Chemical Substances	Oxides ; Trace Elements ; Copper (789U1901C5) ; Iron (E1UOL152H7)
Language	English
Publishing date	2022-06-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2170936-1
ISSN	1743-8977 ; 1743-8977
ISSN (online)	1743-8977
ISSN	1743-8977
DOI	10.1186/s12989-022-00480-z
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Article: Redox sensitive miR-27a/b/Nrf2 signaling in Cr(VI)-induced carcinogenesis

Wang, Lin / Bayanbold, Khaliunaa / Zhao, Lei / Wang, Yifang / Adamcakova-Dodd, Andrea / Thorne, Peter S. / Yang, Hushan / Jiang, Bing-Hua / Liu, Ling-Zhi

Science of the total environment. 2022 Feb. 25, v. 809

2022

Abstract: Hexavalent chromium [Cr(VI)] is a well-known carcinogen that can cause several types of cancer including lung cancer. NF-E2-related factor 2 (Nrf2), the redox sensitive transcription factor, can protect normal cells from a variety of toxicants and ... ...

Abstract	Hexavalent chromium [Cr(VI)] is a well-known carcinogen that can cause several types of cancer including lung cancer. NF-E2-related factor 2 (Nrf2), the redox sensitive transcription factor, can protect normal cells from a variety of toxicants and carcinogens by inducing the expression of cellular protective genes and maintaining redox balance. However, Nrf2 also protects cancer cells from radio- and chemo-therapies and facilitates cancer progression. Although Cr(VI) treatment has been demonstrated to upregulate Nrf2 expression, the mechanisms for Nrf2 regulation upon chronic Cr(VI) exposure remain to be elucidated. We found that Nrf2 was upregulated in BEAS-2B cells exposed to Cr(VI) from 1 to 5 months, and also in Cr(VI)-induced transformed (Cr-T) cells with Cr(VI) treatment for 6 months. We showed that KEAP1, the classic negative regulator of Nrf2, was downregulated after Cr(VI) exposure for 4 months, suggesting that Nrf2 induction by Cr(VI) treatment is through KEAP1 decrease at late stage. To further decipher the mechanisms of Nrf2 upregulation at early stage of Cr(VI) exposure, we demonstrated that miR-27a and miR-27b were redox sensitive miRNAs, since reactive oxygen species (ROS) scavengers induced miR-27a/b expression. After Cr(VI) exposure for 1 month, the expression levels of miR-27a/b was dramatically decreased. The changes of miR-27a/b and their target Nrf2 were confirmed in vivo by mouse model intranasally exposed to Cr(VI) for 12 weeks. Nrf2 was a direct target of miR-27a/b, which acted as tumor suppressors in vitro and in vivo to inhibit tumorigenesis and cancer development of Cr-T cells. The results suggested that the inhibition of miR-27a/b was responsible for Nrf2 upregulation at both early stage and late stage of Cr(VI) exposure. This novel regulation of Nrf2 upon chronic Cr(VI) exposure through redox-regulated miR-27a/b will provide potential targets for preventing and treating Cr(VI)-induced carcinogenesis in the future.
Keywords	carcinogenesis ; carcinogens ; chromium ; environment ; lung neoplasms ; mice ; microRNA ; neoplasm progression ; reactive oxygen species ; transcription factors
Language	English
Dates of publication	2022-0225
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2021.151118
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Article: Biocompatibility of Multi-Imaging Engineered Mesoporous Silica Nanoparticles:

Sweeney, Sean / Adamcakova-Dodd, Andrea / Thorne, Peter S / Assouline, Jose G

Journal of biomedical nanotechnology

2019 Volume 13, Issue 5, Page(s) 544–558

Abstract: Despite potentially serious adverse effects of engineered nanoparticles on maternal health and fetal development, little is known about their transport across the placenta. Human and animal studies are primarily limited ... ...

Abstract	Despite potentially serious adverse effects of engineered nanoparticles on maternal health and fetal development, little is known about their transport across the placenta. Human and animal studies are primarily limited to
Language	English
Publishing date	2019-04-18
Publishing country	United States
Document type	Journal Article
ISSN	1550-7033
ISSN	1550-7033
DOI	10.1166/jbn.2017.2369
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Article ; Online: Immunomodulatory Effects of Subacute Inhalation Exposure to Copper Oxide Nanoparticles in House Dust Mite-Induced Asthma.

Areecheewakul, Sudartip / Adamcakova-Dodd, Andrea / Zacharias, Zeb R / Jing, Xuefang / Meyerholz, David K / Legge, Kevin L / Houtman, Jon C D / O'Shaughnessy, Patrick T / Thorne, Peter S / Salem, Aliasger K

ACS nano

2023 Volume 17, Issue 15, Page(s) 14586–14603

Abstract: It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP inhalation exposure have been less explored. We tested the effect of CuO NP aerosols ...

Abstract	It has been shown that inhalation exposure to copper oxide nanoparticles (CuO NPs) results in pulmonary inflammation. However, immunomodulatory consequences after CuO NP inhalation exposure have been less explored. We tested the effect of CuO NP aerosols on immune responses in healthy, house dust mite (HDM) asthmatic, or allergen immunotherapy (AIT)-treated asthmatic mice (BALB/c, females). The AIT consisted of a vaccine comprising HDM allergens and CpG-loaded nanoparticles (CpG NPs). AIT treatment involved mice being immunized (via subcutaneous (sc) injection; 2 doses) while concomitantly being exposed to CuO NP aerosols (over a 2 week period), starting on the day of the first vaccination. Mice were then sensitized twice by sc injection and subsequently challenged with HDM extract 10 times by intranasal instillation. The asthmatic model followed the same timeline except that no immunizations were administered. All mice were necropsied 24 h after the end of the HDM challenge. CuO NP-exposed healthy mice showed a significant decrease in T
MeSH term(s)	Female ; Mice ; Animals ; Copper ; Inhalation Exposure ; Asthma/chemically induced ; Asthma/therapy ; Pyroglyphidae ; Immunity ; Nanoparticles ; Oxides
Chemical Substances	cupric oxide (V1XJQ704R4) ; cuprous oxide (T8BEA5064F) ; Copper (789U1901C5) ; Oxides
Language	English
Publishing date	2023-07-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.3c01668
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