Maternal and developmental toxicity of polychlorinated diphenyl ethers (PCDEs) in Swiss-Webster mice and Sprague-Dawley rats.
Polychlorinated diphenyl ethers (PCDEs) are industrial byproducts found in many ecosystems at low levels. PCDEs are not markedly toxic to adult rodents, but their developmental toxicity has not previously been examined. We evaluated the maternal and perinatal toxicity of nine PCDE congeners to outbred mice when compounds were administered from gestation day (GD) 6 through GD 15. 2,2',4,4',5,6'-hexaCDE and 2,3',4',6-tetraCDE decreased the number of pups born per female mated and the number of pups surviving per litter born. 2,2',4,4',5,5'-hexaCDE and 2,2',4,5,6'-pentaCDE decreased the number of litters born per female mated, without decreasing postnatal survival. The other PCDEs did not decrease survival either pre- or postnatally. None of the PCDEs caused absence of Harderian glands in surviving offspring at the doses administered. Neither induction of cytochromes P450 nor tissue residues of individual congeners correlated well with developmental toxicity. Three PCDEs were also evaluated in outbred (Sprague-Dawley) rats: 2,2',4,5,6'-pentaCDE and 2,3',4',6-tetraCDE, because of their toxicity to mice; 2,2',4,4',5,5'-hexaCDE, because it should exhibit PCB-like toxicity. Each congener was administered at three dose levels from GD 6 through GD 15. 2,2',4,5,6'-pentaCDE decreased the number of litters born at 100 mg/kg/day, and the survival of pups in litters carried to term, at both 50 and 100 mg/kg per day. Postnatal weight gain was also reduced. In contrast to its action in mice, 2,3',4',6-tetraCDE decreased neither the numbers of litters born nor postnatal survival of rat offspring, but did suppress postnatal weight gain at least through PD 5. As in mice, induction of cytochromes P450 was not well correlated with the developmental toxicity of individual congeners.
Rosiak
K
K
Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana 61801, USA.
Li
M H
MH
Degitz
S J
SJ
Skalla
D W
DW
Chu
I
I
Francis
B M
BM
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D004987:Ethers / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D006243:Harderian Gland / Q000187:drug effects / Q000196:embryology; D008098:Litter Size / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013329:Structure-Activity Relationship; D015430:Weight Gain / Q000187:drug effects
D004987:Ethers; C058905:2,2',4,4',5-pentachlorodiphenyl ether; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1