PCB congeners in the rat brain: selective accumulation and lack of regionalization.
Perturbations in the developing nervous system have been associated with perinatal exposures to polychlorinated biphenyls (PCBs). It remains unclear whether these neurotoxic effects are direct or secondary to other toxic processes. This study was designed to determine which PCB congeners accumulate in the brain as a result of perinatal exposure and if this accumulation is regionally specific. Sprague-Dawley rat dams were dosed by gavage with corn oil or Aroclor 1242 in corn oil (4 or 16 mg/kg/d) on d 10-16 of gestation. At weaning (d 21), one male and one female pup from each litter were euthanatized and three specific regions of the brain (frontal cortex, hippocampus, and caudate putamen) were collected for PCB analysis by gas chromatography. Ten peaks, which represent 10-14 PCB congeners, were detected in all samples. There were no differences in PCB concentration between sexes or among brain regions, but the different congeners differed from each other in degree of bioaccumulation. Brain PCB concentrations increased with increased dose for all congeners except PCB 28 (2,4,4'), which was present at a higher concentration in the lower dose-group. To characterize regionalization of PCBs in the brain further, weanling rats were dosed intravenously with [14C]-PCB 77 (3,3',4,4'-tetrachlorobiphenyl; 0.25 microCi/g; 2.0 micrograms/g) or [14C]-PCB 47 (2,2',4,4'-tetrachhlorobiphenyl; 0.25 microCi/g; 5.3 micrograms/g) in dimethyl sulfoxide (DMSO). Rats were killed after 72 h and the brains were quickly removed and frozen on dry ice. The brains were serially sectioned on a cryostat and the sections (16 microns) subjected to autoradiography (3-5 mo of exposure). The radioactivity was homogeneously distributed in the brain tissue for both PCBs. PCB 77-treated, but not PCB 47-treated, pups showed increased activity in areas with blood vessels present. This was consistent with differences in the blood-brain ratios for PCB 47 and PCB 77, which were determined to be 0.44 and 16.8, respectively.
Ness
D K
DK
Department of Toxicology, Abbott Laboratories, Abbott Park, Illinois.
Schantz
S L
SL
Hansen
L G
LG
D000818:Animals; D001140:Aroclors / Q000493:pharmacokinetics; D001345:Autoradiography; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002849:Chromatography, Gas; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D011078:Polychlorinated Biphenyls / Q000032:analysis / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014018:Tissue Distribution
D001140:Aroclors; D001798:Blood Proteins; C027423:aroclor 1242; D011078:Polychlorinated Biphenyls