title: A 13-week dermal repeat-dose neurotoxicity study of hydrodesulfurized kerosene in rats.
abstract: A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized (HDS) kerosene, a test material that also met the commercial specifications for aviation turbine fuel (jet A). The objectives were to assess the potential for target organ toxicity and neurotoxicity. The HDS kerosene was applied to the shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0 (vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or 495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the high-dose groups were held without treatment for 4 weeks to assess recovery. Standard parameters of toxicity were investigated during the in-life phase. At necropsy, organs were weighed and selected tissues were processed for microscopic evaluation. Neurobehavioral evaluations included tests of motor activity and functional observations that were conducted pretest, at intervals during the exposure period and after recovery. No test substance-related effects on mortality, clinical observations (except dermal irritation), body weight, or clinical chemistry values were observed. A dose-related increase in skin irritation, confirmed histologically as minimal, was evident at the dosing site. The only statistically significant change considered potentially treatment related was an increase in the neutrophil count in females at 13 weeks. No test article-related effects were observed in the neurobehavioral assessments or gross or microscopic findings in the peripheral or central nervous system tissues in any of the dose groups. Excluding skin irritation, the no observed adverse effect level value for all effects was considered 495 mg/kg/d.
authors.affiliation: American Petroleum Institute, Washington, DC 20005, USA. Email: whiter@api.org.
authors.forename: Rudolph
authors.initials: R
authors.lastname: Breglia
authors.forename: Quang
authors.initials: Q
authors.lastname: Bui
authors.forename: Donald
authors.initials: D
authors.lastname: Burnett
authors.forename: Francis
authors.initials: F
authors.lastname: Koschier
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lapadula
authors.forename: Paula
authors.initials: P
authors.lastname: Podhasky
authors.forename: Ceinwen
authors.initials: C
authors.lastname: Schreiner
authors.forename: Russell
authors.initials: R
authors.lastname: White
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007648:Kerosene / Q000633:toxicity*; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology*; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012871:Skin Diseases / Q000209:etiology / Q000473:pathology*; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D007648:Kerosene
keywords: CAS number 64742-81-0; aviation turbine fuel; dermal application; hydrodesulfurized; jet A; kerosene; kerosine (petroleum); neurotoxicity assessment; repeated dose toxicity; target organ toxicity