title: Limited effects of ozone exposure during pregnancy on physical and neurobehavioral development of CD-1 mice.
abstract: Only a few studies have attempted to assess in laboratory rodents the maternal toxicity and behavioral changes in offspring caused by prenatal exposure to ozone (O3). In particular, no data are available concerning the behavioral development of mouse offspring after maternal exposure, despite the fact that increasing use is made of this species in behavioral teratology studies for reasons both of economy and in order to increase the effectiveness of subsequent higher-tier studies (e.g., of treatment-genotype interactions). In the present work, female CD-1 mice were exposed during pregnancy (Days 7-17) to different O3 concentrations (0, 0.4, 0.8, or 1.2 ppm); to avoid confounding by postnatal maternal effects, all litters were assigned shortly after birth to foster dams neither treated nor handled during pregnancy. The dams' food and water intake and body weight gain were depressed in a concentration-dependent fashion. Tolerance to these effects developed during continuing exposure; such tolerance was faster in the case of food than water intake. Several measures of reproductive performance, such as proportion of pregnancies carried to term, litter size, sex ratio, frequency of stillbirth, and neonatal mortality, failed to show differences between control and O3 animals. Postnatal body weight gain was slightly but significantly depressed in the 1.2 ppm offspring. Otherwise, the somatic development of O3 pups was indistinguishable from that of controls, save for a delay in eye opening; this effect, however, failed to show a significant concentration dependence. Negative results were obtained in a wide range of assessments concerning (i) the development of various reflexes and responses ("Fox battery") from birth to Day 18; (ii) ultrasonic emissions on Postnatal Days 3, 7, and 11; and (iii) activity, habituation, response to an unfamiliar object, and hyperactivity produced by a monoaminergic stimulant (d-amphetamine) at 60-61 days. The present data differ from those of a previous study on rats raised by their biological mothers after gestational exposure to O3 (1 and 1.5 ppm), which showed a substantial impairment in somatic and neurobehavioral development (R. Kavlock, E. Meyer, and C. T. Grabowski, 1980, Toxicol. Lett. 5, 3-9). This difference, be it due to species factors, to postnatal maternal effects, or to the time of occurrence of maximal O3 effects (e.g., on food and water intake) after the onset of exposure and before adaptation or tolerance, may provide significant cues for the understanding of O3 effects in pregnant and developing organisms.
authors.affiliation: Section of Behavioral Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bignami
authors.forename: B
authors.initials: B
authors.lastname: Musi
authors.forename: G
authors.initials: G
authors.lastname: Dell'Omo
authors.forename: G
authors.initials: G
authors.lastname: Laviola
authors.forename: E
authors.initials: E
authors.lastname: Alleva
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects*; D010126:Ozone / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D012018:Reflex / Q000187:drug effects; D014828:Vocalization, Animal / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D010126:Ozone; D003913:Dextroamphetamine