Inhibition of 3,3',4,4',5-pentachlorobiphenyl-induced fetal cleft palate and immunotoxicity in C57BL/6 mice by 2,2',4,4',5,5'-hexachlorobiphenyl.
3,3',4,4',5-Pentachlorobiphenyl (pentaCB) caused a dose-dependent induction of fetal cleft palate in offspring from pregnant C57BL/6 mice exposed to a single dose (783 or 1044 micrograms/kg) of this compound on gestation day 10. In contrast, 2,2',4,4',5,5'-hexaCB did not cause cleft palate at a dose of 271 mg/kg and, in pregnant mice cotreated with 2,2',4,4',5,5'-hexaCB (271 mg/kg) plus 783 or 1044 micrograms/kg 3,3',4,4',5-pentaCB, fetal cleft palate formation was significantly inhibited. 3,3',4,4',5-PentaCB (6 micrograms/kg) also inhibited the splenic plaque-forming cell (PFC) response and serum IgM levels in C57BL/6 mice treated with the T cell-independent antigen trinitrophenyl-lipopolysaccharide. At doses as high as 72 mg/kg, 2,2',4,4'-5,5'-hexaCB was not immunotoxic; however, in mice cotreated with a immunotoxic dose of 3,3',4,4',5-pentaCB plus different doses of 2,2',4,4',5,5'-hexaCB (18, 36 and 72 mg/kg), there was a dose-dependent inhibition of 3,3',4,4',5-pentaCB-induced immunotoxicity. These non-additive (antagonistic) interactions of prototypical polychlorinated biphenyl (PCB) congeners may be an important consideration in development of a toxic equivalency factor approach for hazard and risk assessment of PCB mixtures.
Zhao
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F
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station 77843-4466, USA.
Mayura
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K
Harper
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N
Safe
S H
SH
Phillips
T D
TD
D000818:Animals; D002972:Cleft Palate / Q000139:chemically induced* / Q000196:embryology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D000922:Immunotoxins / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011078:Polychlorinated Biphenyls / Q000037:antagonists & inhibitors / Q000627:therapeutic use* / Q000633:toxicity*; D011247:Pregnancy; D018675:Toxicity Tests
D000922:Immunotoxins; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl