Metabolism of 1-nitropyrene in mice: transport across the placenta and mammary tissues.
The distribution and metabolism of the environmental pollutant 1-nitropyrene was studied in C57B1/6N mice following oral or intraperitoneal dosing. When administered by gavage, 1-nitropyrene and its metabolites demonstrated biphasic elimination kinetics from the blood, with half-lives of 0.3 and 1.8 days and a distribution volume of 74 ml. Intraperitoneal administration resulted in similar biphasic elimination, with half-lives of 0.5 and 3 days and a distribution volume of 98 ml. Treating pregnant C57B1/6N (C3H sire) mice by gavage resulted in similar absorption and elimination kinetics of 1-nitropyrene and metabolites, except that the distribution volume increased to 123 ml. 1-Nitropyrene and/or its metabolites (0.7% of the administered dose) crossed the placenta and accumulated in the fetuses and amniotic fluid, with both C-oxidized and nitroreduced metabolites being detected. Suckling neonates accumulated 1-nitropyrene and its metabolites when their dams were administered 1-nitropyrene by gavage. Each neonate received approximately 0.1% of the administered dose and demonstrated the presence of both C-oxidized and nitroreduced metabolites. These results demonstrate that this environmental pollutant is capable of crossing the placenta or mammary tissues to expose the offspring to a potentially genotoxic compound.
Howard
P C
PC
Department of Environmental Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4940, USA.
Consolo
M C
MC
Dooley
K L
KL
Beland
F A
FA
D000284:Administration, Oral; D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D000833:Animals, Suckling; D001692:Biological Transport; D001774:Blood Chemical Analysis; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D010084:Oxidation-Reduction; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011721:Pyrenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D013056:Spectrophotometry, Ultraviolet
D009153:Mutagens; D011721:Pyrenes; C032668:1-nitropyrene