title: Subchronic and developmental toxicity of aromatic extracts.
abstract: Aromatic extracts (AEs; distillate AEs [DAEs] and residual AEs [RAEs]) are complex, highly viscous liquid petroleum streams with variable compositions derived by extraction of aromatic compounds from distillate and residual petroleum fractions from a vacuum distillation tower, respectively. The DAEs generally contain significant amounts of polycyclic aromatic compounds (PACs) and are carcinogenic. The RAEs typically contain lower concentrations of biologically active PACs. The PACs in refinery streams can cause effects in repeated-dose and developmental toxicity studies. In a 13-week dermal study, light paraffinic DAE had several dose-related effects involving multiple organs; no-observed-effect level was <5 mg/kg/d, with no overt toxicity. Predicted dose-responses at 10% (PDR10s), modeled doses causing a 10% effect on sensitive end points based on PAC content, ranged from 25 to 78 mg/kg/d for untested paraffinic DAEs. The no observed adverse effect level (NOAEL) for developmental toxicity for light paraffinic DAE was 5 mg/kg/d. Statistically significant developmental effects at higher doses were associated with maternal effects. The PDR10s for developmental toxicity of paraffinic DAEs ranged from 7 to >2000 mg/kg/d, reflecting differences due to variation in PACs. The NOAELs for RAEs were 500 mg/kg for 90-day studies and 2000 mg/kg for developmental toxicity. Reproductive toxicity is not considered to be a sensitive end point for AEs based on the toxicity tests with DAEs, RAEs, and other PAC-containing petroleum substances. In vivo micronucleus tests on heavy paraffinic DAE, RAEs, and a range of other petroleum substances have been negative. The exception to this general trend was a marginally positive response with light paraffinic DAE. Most DAEs are considered unlikely to produce chromosomal effects in vivo.
authors.affiliation: DalbeyTox, LLC, 860 Penns Way, West Chester, PA 19382, USA. Email: dalbeytox@verizon.net.
authors.forename: Walden E
authors.initials: WE
authors.lastname: Dalbey
authors.forename: Richard H
authors.initials: RH
authors.lastname: McKee
authors.forename: Katy Olsavsky
authors.initials: KO
authors.lastname: Goyak
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Charlap
authors.forename: Craig
authors.initials: C
authors.lastname: Parker
authors.forename: Russell
authors.initials: R
authors.lastname: White
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D019055:No-Observed-Adverse-Effect Level; D010578:Petroleum / Q000032:analysis / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D059550:Toxicity Tests, Subchronic
chemical_list: D002273:Carcinogens; D010578:Petroleum; D011084:Polycyclic Aromatic Hydrocarbons
keywords: aromatic extract; dermal; developmental; micronucleus; petroleum; rat; subchronic; toxicity