Mechanistic and dose considerations for supporting adverse pulmonary physiology in response to formaldehyde.
Induction of airway hyperresponsiveness and asthma from formaldehyde inhalation exposure remains a debated and controversial issue. Yet, recent evidences on pulmonary biology and the pharmacokinetics and toxicity of formaldehyde lend support for such adverse effects. Specifically, altered thiol biology from accelerated enzymatic reduction of the endogenous bronchodilator S-nitrosoglutathione and pulmonary inflammation from involvement of Th2-mediated immune responses might serve as key events and cooperate in airway pathophysiology. Understanding what role these mechanisms play in various species and lifestages (e.g., child vs. adult) could be crucial for making more meaningful inter- and intra-species dosimetric extrapolations in human health risk assessment.
National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Washington, DC 20460, USA. Thompson.Chad@epa.gov
Chad M
CM
Thompson
Ravi P
RP
Subramaniam
Roland C
RC
Grafström
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000633:toxicity*; D006801:Humans; D007509:Irritants / Q000633:toxicity*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D018570:Risk Assessment; D026422:S-Nitrosoglutathione / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
D007509:Irritants; D005557:Formaldehyde; D026422:S-Nitrosoglutathione