LIMITED EFFECTS OF OZONE EXPOSURE DURING PREGNANCY ON PHYSICAL AND NEUROBEHAVIORAL DEVELOPMENT OF CD-1 MICE

Only a few studies have attempted to assess in laboratory rodents the maternal toxicity and behavioral changes in offspring caused by prenat al exposure to ozone (O-3). In particular, no data are available conce rning the behavioral development of mouse offspring after maternal exp osure, despite the fact that increasing use is made of this species in behavioral teratology studies for reasons both of economy and in orde r 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 O-3 con centrations (0, 0.4, 0.8, or 1.2 ppm); to avoid confounding by postnat al maternal effects, all litters were assigned shortly after birth to foster dams neither treated nor handled during pregnancy. The dams' fo od and water intake and body weight gain were depressed in a concentra tion-dependent fashion. Tolerance to these effects developed during co ntinuing exposure; such tolerance was faster in the case of food than water intake. Several measures of reproductive performance, such as pr oportion of pregnancies carried to term, litter size, sex ratio, frequ ency of stillbirth, and neonatal mortality, failed to show differences between control and O-3 animals. Postnatal body weight gain was sligh tly but significantly depressed in the 1.2 ppm offspring. Otherwise, t he somatic development of O-3 pups was indistinguishable from that of controls, save for a delay in eye opening; this effect, however, faile d to show a significant concentration dependence. Negative results wer e obtained in a wide range of assessments concerning (i) the developme nt of various reflexes and responses (''Fox battery'') from birth to D ay 18; (ii) ultrasonic emissions on Postnatal Days 3, 7, and 11; and ( iii) activity, habituation, response to an unfamiliar object, and hype ractivity produced by a monoaminergic stimulant (d-amphetamine) at 60- 61 days. The present data differ from those of a previous study on rat s raised by their biological mothers after gestational exposure to O-3 (1 and 1.5 ppm), which showed a substantial impairment in somatic and neurobehavioral development (R. Kavlock, E. Meyer, and C. T. Grabowsk i, 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 O-3 effects (e.g., on food and water intake) after the onse t of exposure and before adaptation or tolerance, may provide signific ant cues for the understanding of O-3 effects in pregnant and developi ng organisms. (C) 1994 Academic Press, Inc.