title: Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats.
abstract: Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoline alone (E0) and gasoline with 15% or 85% ethanol (E15 and E85, respectively). Rat dams were exposed for 6.5h daily to the vapors at concentrations of 0, 3000, 6000, or 9000 ppm in inhalation chambers from gestational day (GD) 9 through 20. Cage controls (offspring of non-exposed dams that remained in the animal facility during these exposures) were also assessed in the E0 experiment, but showed no consistent differences from the offspring of air-exposed controls. Offspring were tested as adults with trace fear conditioning, Morris water maze, or appetitive operant responding. With fear conditioning, no significant effects were observed on cue or context learning. In the water maze, there were no differences in place learning or escaping to a visible platform. However, during the reference memory probe (no platform) male rats exposed prenatally to E85 vapor (6000 and 9000 ppm) failed to show a bias for the target quadrant. Across studies, females (treated and some controls) were less consistent in this measure. Males showed no differences during match-to-place learning (platform moved each day) in any experiment and females showed only transient differences in latency and path length in the E0 experiment. Similarly, no differences were observed in delayed match-to-sample operant performance of E0 males or females; thus this test was not used to evaluate effects of E15 or E85 vapors. During choice reaction time assessments (only males were tested) decision and movement times were unimpaired by any prenatal exposure, while anticipatory responses were increased by vapors of E0 (9000 ppm) and E15 (6000 and 9000 ppm), and the latter group also showed reduced accuracy. E85 vapors did not disrupt any choice reaction time measure. Finally, no response inhibition deficit was observed in a differential reinforcement of low rate (DRL) response schedule in males or females in the E15 or E85 experiments. In summary, prenatal exposure to these fuel blends produced few deficits in adult offspring on these cognitive tests. Significant effects found during a water maze probe trial and choice reaction time tests were observed at vapor concentrations of 6000 ppm or higher, a concentration that is 4-6 orders of magnitude higher than those associated with normal automotive fueling operations and garages. Similar effects were not consistently observed in a previous study of inhaled ethanol, and thus these effects cannot be attributed to the concentration of ethanol in the mixture.
authors: Toxicity Assessment Division, MD B105-04, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: oshiro.wendy@epa.gov.
authors: W M
authors: WM
authors: Oshiro
authors: Toxicity Assessment Division, MD B105-04, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: beasley.tracey@epa.gov.
authors: T E
authors: TE
authors: Beasley
authors: Toxicity Assessment Division, MD B105-04, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: mcdaniel.kathy@epa.gov.
authors: K L
authors: KL
authors: McDaniel
authors: Environmental Public Health Division, MD B105-02, National Health Effects and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: evansky.paul@epa.gov.
authors: P A
authors: PA
authors: Evansky
authors: Toxicity Assessment Division, MD B105-04, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: sam506@gmail.com.
authors: S A
authors: SA
authors: Martin
authors: Toxicity Assessment Division, MD B105-04, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: moser.ginger@epa.gov.
authors: V C
authors: VC
authors: Moser
authors: Toxicity Assessment Division, MD B105-04, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: gilbert.mary@epa.gov.
authors: M E
authors: ME
authors: Gilbert
authors: Toxicity Assessment Division, MD B105-04, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: bushnell.philip@epa.gov.
authors: P J
authors: PJ
authors: Bushnell
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced*; D003214:Conditioning, Classical / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005239:Fear / Q000187:drug effects; D005260:Female; D005742:Gasoline / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule
chemical_list: D005742:Gasoline; D000431:Ethanol
keywords: Biofuels; Development; Impulsivity; Learning; Memory; Reaction time