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Cited by 41Prenatal Substance Exposure EffectsSmoking Behavior and CessationPharmacological Effects and Toxicity Studies

In Utero and Lactation Exposure of Rats to 1R4F Reference Cigarette Mainstream Smoke: Effect on Prenatal and Postnatal Development

Gaworski, C. L.·2004·Toxicological Sciences
DOI 10.1093/toxsci/kfh083
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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.

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  • Rodent studies suggest prenatal nicotine exposure delays reflex maturation, including negative geotaxis and surface righting, and causes long-lasting changes in filtering auditory information.

    “rodent studies suggest that prenatal nicotine exposure delays maturation of reflexes, including negative geotaxis and surface righting (measures of limb coordination and locomotor development), as well as causing long-lasting alterations in filtering auditory information.”

    From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [178]

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Authors
Gaworski, C. L.
Affiliations
Altria (United States) (US)
Corresponding author
Gaworski, C. L.
Venue
Toxicological Sciences
Publisher
Oxford University Press (OUP)
Published
2004-01-21
Volume
79
Issue
1
Pages
157-169
ISSN
1096-0929 (ISSN-L)
DOI
10.1093/toxsci/kfh083
OpenAlex
W2100012493
Cited by
41
References
57
Citations by year
2026: 1 · 2023: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 7 · 2012: 3
FWCI
0.59
Type
journal article
Language
en
Open access
closed
Locations
  • Toxicological Sciences (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Keywords
cigarette smoke, prenatal exposure, maternal smoking, birth weight, neonatal growth, neurobehavioral development, total particulate matter, nicotine, cotinine, carboxyhemoglobin, gestational toxicity, developmental neurotoxicity, rodent models
MeSH terms
Administration, Inhalation, Animals, Animals, Newborn, Behavior, Animal, Carbon Monoxide, Carboxyhemoglobin, Cotinine, Drug Evaluation, Preclinical, Female, Lactation, Male, Nicotine, Particle Size, Pregnancy, Pregnancy, Animal, Prenatal Exposure Delayed Effects, Reproduction, Respiratory System, Sexual Behavior, Animal, Smoke, Nicotiana, Rats, Sprague-Dawley, Maternal Exposure, Paternal Exposure, Rats

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