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In utero and lactation exposure of rats to 1R4F reference cigarette mainstream smoke: effect on prenatal and
C L Gaworski1, E L Carmines, A S Faqi
1Philip Morris USA, Richmond, Virginia 23224, USA. charles.l.gaworski@pmusa.com
Insights
Maternal smoking during pregnancy in rats reduced offspring birth weight and growth. However, neurobehavioral tests did not detect cognitive or behavioral deficits in the F(1) generation.
Area of Science:
- Toxicology
- Developmental Biology
- Neuroscience
Background:
- Childhood cognitive and behavioral deficits are linked to maternal smoking during pregnancy.
- Animal models are crucial for investigating these effects.
- U.S. FDA guidelines provide a framework for reproductive and neurotoxicity evaluations.
Purpose of the Study:
- To investigate the effects of maternal cigarette smoke exposure on offspring development and neurobehavior in a rat model.
- To evaluate potential cognitive and behavioral deficits in the F(1) generation.
Main Methods:
- Sprague-Dawley rats were exposed to whole mainstream smoke total particulate matter (TPM) via nose-only inhalation.
- Exposure concentrations were 150, 300, or 600 mg/m(3) for parental rats.
- Offspring (F(1) generation) were assessed for physical growth, developmental landmarks, and neurobehavioral effects through postnatal day 65.
Main Results:
- Parental exposure confirmed by increased carboxyhemoglobin, nicotine, and cotinine in blood, and respiratory tract histopathology.
- Maternal toxicity (decreased weight gain) observed at 300 and 600 mg TPM/m(3).
- Significant decreases in F(1) birth weight and growth at 600 mg TPM/m(3); however, no adverse neurobehavioral effects were detected.
Conclusions:
- Maternal exposure to high levels of cigarette smoke during gestation and lactation retards neonatal growth in rats.
- Current developmental and neurobehavioral testing methods may not be sensitive enough to detect subtle effects following parental smoke exposure.
- Further research may be needed to identify sensitive endpoints for evaluating neonatal behavioral effects.
Abstract:
Childhood cognitive and behavioral deficits have been reported in children born to mothers who smoked during pregnancy (Institute of Medicine, 2001). To investigate these potential responses in an animal model, reproductive and neurotoxicity evaluations based on the U.S. FDA guidelines were used to examine the offspring of male and female Sprague-Dawley rats exposed 2 h/day, 7 days/week by nose-only inhalation to whole mainstream smoke total particulate matter (TPM). Concentrations of 150, 300, or 600 mg/m(3) were used (males: 4 weeks prior to and during mating; and females: 2 weeks prior to mating, during mating, and through weaning at postnatal day 21). Sham air controls receiving filtered air and cage controls were also maintained. F(1) rats were weighed, identified by gender, examined for clinical signs of toxicity, and evaluated for neurobehavioral effects through postnatal day 65. Parental exposure was evidenced by smoke concentration-related increases in blood carboxyhemoglobin, nicotine, and cotinine and by characteristic cigarette smoke-related rodent respiratory tract histopathology. Also, nicotine and cotinine were found in F(1) blood through the lactation period. Maternal toxicity occurred at concentrations of 300 and 600 mg TPM/m(3), where total body weight gain during gestation was significantly (p < or = 0.05) decreased compared to sham controls. While smoke concentration-related decreases in F(1) birth weight and growth were evident (600 mg TPM/m(3), significantly different from sham at all time points), no adverse effects on developmental landmarks, including age at vaginal patency or preputial separation, motor activity, acoustic startle response or learning, and memory, were observed in the F(1) generation. This study confirmed that maternal exposure to high levels of mainstream cigarette smoke during gestation and lactation reduces birth weight and retards growth in the rat neonate; however, the developmental and neurobehavioral testing methodologies employed did not appear to be sensitive for an evaluation of neonatal behavioral effects following parental smoke exposure.
