Non-coplanar 2,2',3,3',4,4',5,5',6,6'-decachlorobiphenyl (PCB 209) did not induce cytochrome P450 enzyme activities in primary cultured rat hepatocytes, was not genotoxic, and did not exhibit endocrine-modulating activities.
2,2',3,3',4,4',5,5',6,6'-Decachlorobiphenyl (PCB 209) is a fully chlorinated, non-coplanar biphenyl. To demonstrate that PCB 209 is not likely to exhibit human health hazards common to coplanar PCBs it was tested for cytochrome P450 (P450) enzyme induction potentials, genetic toxicity, and endocrine-modulating activity. PCB 209 (dose from 0.005 to 5000 ng/mL) did not significantly induce P450 CYP1A, 2A, 2B, 3A, or 4A enzyme activities in primary cultured rat hepatocytes. In contrast, Aroclor 1260, a PCB mixture that contains approximately 60% chlorine by weight, showed significant induction of P450 CYP1A, 2A, 2B, and 3A within the same dose range. PCB 209 (dose from 100 to 5000 microg/plate) was negative in the bacterial mutagenicity (Ames) test in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 or in Eschericia coli strain WP2uvrA. PCB 209 (dose from 25 to 150 microg/mL) was also negative for forward mutations at the thymidine kinase (TK+/-) locus of L5178Y mouse lymphoma cells. The Ames and the mouse lymphoma assays were both conducted in the absence and presence of rat liver S9 fraction. PCB 209 (dose from 500 to 2000 mg/kg by single dose oral gavage) did not induce an increase in the frequency of micronuclei in polychromatic erythrocytes in mouse bone marrow in vivo. PCB 209 did not induce estrogenic effects when administered by gavage to ovariectomized adult female rats at 500 and 1000 mg/kg for 4 days, nor did it produce alterations consistent with endocrine-modulating activity in adult intact male rats when administered by gavage at 500 and 1000 mg/kg for 15 consecutive days.
Han
Xing
X
DuPont Haskell Global Centers for Health & Environmental Sciences, Newark, DE 19714, USA. xing.han@dupont.com
O'Connor
John C
JC
Donner
E Maria
EM
Nabb
Diane L
DL
Mingoia
Robert T
RT
Snajdr
Suzanne I
SI
Clarke
Jane J
JJ
Kaplan
A Michael
AM
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000493:pharmacokinetics / Q000633:toxicity*; D004790:Enzyme Induction; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D052244:Endocrine Disruptors; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C005381:decachlorobiphenyl