Teratogenicity and developmental toxicity of carbon monoxide in protein-deficient mice.
Experiments were carried out to determine the teratogenicity and developmental toxicity of carbon monoxide (CO) in mice fed protein-deficient diets. Pregnant CD-1 mice were fed 27 (control), 16, 8, or 4% protein diets throughout gestation and each group was exposed to 0 (control), 65, 125, 250, or 500 ppm of CO from gestation days 8-18. The CO exposure was continuous except for daily watering, feeding or cage changing. The animals were killed on gestation day 18. Pregnancy status of the dams was examined. Fetuses were examined for gross and skeletal malformations. The percentages of dead or resorbed fetuses and of grossly malformed fetuses per litter were related to the CO exposure levels and inversely related to the dietary protein levels. All levels of CO and 8 or 4% protein diets significantly decreased the fetal weight of normal fetuses. The most commonly seen gross malformations were brachygnathia accompanied by protruding tongue, microstomia, microcephaly, open mouth, or open eyes. Most of the grossly malformed fetuses also had dry, bleached and wrinkled skin. An increased incidence of skull (interparietal or supraoccipital), and jaw (mandible or premaxilla) malformation; wavy ribs and scoliosis of spine; and limb unossifications were observed in the litters of dams fed protein-deficient diet and all levels of CO exposure. Malformed litters in each protein diet were related to CO exposure levels. The data suggest that CO is teratogenic under protein-deficient conditions. Protein deficiency had additive effect on CO teratogenicity and synergistic effect on fetal mortality. Special groups at risk may include cigarette or marijuana smokers and malnourished or undernourished populations.
Singh
J
J
Department of Biology, Stillman College, Tuscaloosa, Alabama 35403.
Aggison
L
L
Moore-Cheatum
L
L
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002248:Carbon Monoxide / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005313:Fetal Death; D005327:Fetal Resorption; D051379:Mice; D011247:Pregnancy; D011488:Protein Deficiency; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens; D002248:Carbon Monoxide