ToxSci Advance Access originally published online on January 17, 2008
Toxicological Sciences 2008 102(2):383-391; doi:10.1093/toxsci/kfn009
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Evidence for Carbon Monoxide as the Major Factor Contributing to Lower Fetal Weights in Rats Exposed to Cigarette Smoke
* Philip Morris USA, Center for Research and Technology, Richmond, Virginia 23219
IIT Research Institute, 10 West 35th Street, Chicago, Illinois 60616
1 To whom correspondence should be addressed at Philip Morris USA, Center for Research and Technology, 601 East Jackson Street, Richmond, VA 23219. Fax: (804) 335-2090. E-mail: edward.l.carmines{at}pmusa.com.
Received September 18, 2007; accepted December 11, 2007
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Abstract |
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One of the major effects of cigarette smoking during pregnancy is bearing a child with lower birth weight. It has previously been demonstrated under experimental conditions in rats that exposure to reference cigarette smoke results in reduced birth weight (E. L. Carmines et al., 2003, Toxicol. Sci. 75, 134–147; C. L. Gaworski et al., 2004, Toxicol. Sci. 79, 157–169). The role of various smoke constituents on lower birth weight was evaluated by exposing time-pregnant Sprague-Dawley rats at the concentrations found in cigarette smoke. The rats were exposed for 2 h/day 7 days/week by nose-only inhalation. The target concentrations were designed to produce the same plasma levels of biomarkers as exposure to 2R4F reference cigarette smoke at a concentration of 600 mg/m3 total particulate matter. The smoke constituents evaluated included carbon monoxide (CO), nicotine, and a mixture of aldehydes (acrolein, acetaldehyde, and formaldehyde). The smoke constituents were tested individually as well as in mixtures to evaluate potential interactions. Exposure to cigarette smoke during gestation produced a reduction in both maternal body weight gain and fetal weights. Exposure to nicotine reduced maternal body weight gain but had no effect on fetal weight. Exposure to CO had no effect on maternal body weight gain but reduced fetal weight to a degree comparable to cigarette smoke. Exposure to a mixture of aldehydes (acrolein, acetaldehyde, and formaldehyde) had no effect on either maternal body weight gain or fetal weight. Exposure to mixtures of nicotine and CO or nicotine, CO, and aldehydes did not demonstrate any interactions. The results of this study suggest that the observed reduction in fetal weight after exposure to cigarette smoke in rats is due to CO toxicity and not nicotine toxicity.
Key Words: cigarette smoke; low birth weight; nicotine; carbon monoxide.