title: Dermal Exposure to Cumene Hydroperoxide: Assessing Its Toxic Relevance and Oxidant Potential.
abstract: Cumene hydroperoxide (CHP) is a high production volume chemical that is used to generate phenol and acetone. Dermal exposure to CHP was hypothesized to result in systemic tissue toxicity, production of free radicals, and consequent decrease in plasma antioxidant levels. To evaluate the hypothesis and characterize the toxicity of CHP, male and female B6C3F1/N mice and F344/N rats were exposed to varying doses of CHP applied topically for 14 or 90 days. No significant changes in survival or body weight of mice and rats were observed following 14 days of exposure. However, 90 days of CHP exposure at the high dose (12 mg/kg) triggered a significant decrease (-15%) in the body weight of the male rat group only. Irritation of the skin was observed at the site of application and was characterized by inflammation and epidermal hyperplasia. In treated animals, histology of liver tissue, free radical generation, and antioxidant levels in blood plasma were not significantly changed as compared to the corresponding controls. Consistent with the lack of systemic damage, no increase in micronucleated erythrocytes was seen in peripheral blood. In conclusion, topical CHP application caused skin damage only at the application site and did not cause systemic tissue impairment.
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA cynthia.rider@nih.gov.
authors.forename: Cynthia V
authors.initials: CV
authors.lastname: Rider
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
authors.forename: Po
authors.initials: P
authors.lastname: Chan
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
authors.forename: Ron A
authors.initials: RA
authors.lastname: Herbert
authors.affiliation: Division of Intramural Research, Biostatistics & Computational Biology Branch, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.affiliation: Battelle Memorial Institute, Columbus, Ohio, USA.
authors.forename: Laurene M
authors.initials: LM
authors.lastname: Fomby
authors.affiliation: Battelle Memorial Institute, Columbus, Ohio, USA.
authors.forename: Milton R
authors.initials: MR
authors.lastname: Hejtmancik
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
authors.forename: Kristine L
authors.initials: KL
authors.lastname: Witt
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
authors.forename: Suramya
authors.initials: S
authors.lastname: Waidyanatha
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, North Carolina, USA.
authors.forename: Greg S
authors.initials: GS
authors.lastname: Travlos
authors.affiliation: Division of Intramural Research, Inflammation, Immunity, and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Kadiiska
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D016877:Oxidants / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000187:drug effects*
chemical_list: D001555:Benzene Derivatives; D016877:Oxidants; C007164:cumene hydroperoxide
keywords: Ames assay; industrial chemical; oxidizing agent; skin irritant