Sex-specific respiratory and systemic endocrine effects of acute acrolein and trichloroethylene inhalation

Alewel, Devin I.; Jackson, Thomas W.; Vance, Samuel A.; Schladweiler, Mette C.; Evansky, Paul A.; Henriquez, Andres R.; Grindstaff, Rachel; Gavett, Stephen H.; Kodavanti, Urmila P.

doi:10.1016/j.toxlet.2023.05.005

Sex-specific respiratory and systemic endocrine effects of acute acrolein and trichloroethylene inhalation

Journal Article · Tue May 16 04:00:00 EDT 2023 · Toxicology Letters

DOI:https://doi.org/10.1016/j.toxlet.2023.05.005· OSTI ID:2425798

^[1]; ^[1]; Vance, Samuel A. ^[1]; Schladweiler, Mette C. ^[1]; Evansky, Paul A. ^[1]; ^[2]; Grindstaff, Rachel ^[1]; Gavett, Stephen H. ^[1]; ^[1]

U.S. Environmental Protection Agency (EPA), Research Triangle Park, NC (United States)
U.S. Environmental Protection Agency (EPA), Research Triangle Park, NC (United States); Environmental Health Science and Research Bureau, Ontario (Canada)

Acrolein and trichloroethylene (TCE) are priority hazardous air pollutants due to environmental prevalence and adverse health effects; however, neuroendocrine stress-related systemic effects are not characterized. Comparing acrolein, an airway irritant, and TCE with low irritancy, we hypothesized that airway injury would be linked to neuroendocrine-mediated systemic alterations. Male and female Wistar-Kyoto rats were exposed nose-only to air, acrolein or TCE in incremental concentrations over 30 min, followed by 3.5-hr exposure to the highest concentration (acrolein - 0.0, 0.1, 0.316, 1, 3.16 ppm; TCE - 0.0, 3.16, 10, 31.6, 100 ppm). Real-time head-out plethysmography revealed acrolein decreased minute volume and increased inspiratory-time (males>females), while TCE reduced tidal-volume. Acrolein, but not TCE, inhalation increased nasal-lavage-fluid protein, lactate-dehydrogenase activity, and inflammatory cell influx (males>females). Neither acrolein nor TCE increased bronchoalveolar-lavage-fluid injury markers, although macrophages and neutrophils increased in acrolein-exposed males and females. Systemic neuroendocrine stress response assessment indicated acrolein, but not TCE, increased circulating adrenocorticotrophic hormone, and consequently corticosterone, and caused lymphopenia, but only in males. Acrolein also reduced circulating thyroid-stimulating hormone, prolactin, and testosterone in males. Furthermore, acute acrolein inhalation resulted in sex-specific upper respiratory irritation/inflammation and systemic neuroendocrine alterations linked to hypothalamic-pituitary-adrenal axes activation, which is critical in mediating extra-respiratory effects.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States); U.S. Environmental Protection Agency (EPA), Research Triangle Park, NC (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0014664

OSTI ID:: 2425798

Journal Information:: Toxicology Letters, Journal Name: Toxicology Letters Journal Issue: C Vol. 382; ISSN 0378-4274

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
Acrolein
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Sex-specific respiratory and systemic endocrine effects of acute acrolein and trichloroethylene inhalation

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