PMID- 18190939
OWN - NLM
STAT- MEDLINE
DCOM- 20080505
LR  - 20161124
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 227
IP  - 3
DP  - 2008 Mar 15
TI  - Relative potency based on hepatic enzyme induction predicts immunosuppressive 
      effects of a mixture of PCDDS/PCDFS and PCBS.
PG  - 477-84
LID - 10.1016/j.taap.2007.11.018 [doi]
AB  - The toxic equivalency factor (TEF) approach was employed to compare immunotoxic 
      potency of mixtures containing polychlorinated dibenzo-p-dioxins, polychlorinated 
      dibenzofurans and polychlorinated biphenyls relative to 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), using the antibody response to sheep 
      erythrocytes (SRBC). Mixture-1 (MIX-1) contained TCDD, 
      1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,7,8-tetrachlorodibenzofuran 
      (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 
      2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), and 
      1,2,3,4,6,7,8,9-octachlorodibenzofuran (OCDF). Mixture-2 (MIX-2) contained MIX-1 
      and the following PCBs, 3,3',4,4'-tetrachlorobiphenyl (IUPAC No. 77), 
      3,3',4,4',5-pentachlorobiphenyl (126), 3,3',4,4',5,5N-hexachlorobiphenyl (169), 
      2,3,3',4,4'-pentachlorobiphenyl (105), 2,3',4,4',5-pentachlorobiphenyl (118), and 
      2,3,3',4,4',5-hexachlorobiphenyl (156). The mixture compositions were based on 
      relative chemical concentrations in food and human tissues. TCDD equivalents 
      (TEQ) of the mixture were estimated using relative potency factors from hepatic 
      enzyme induction in mice [DeVito, M.J., Diliberto, J.J., Ross, D.G., Menache, 
      M.G., Birnbaum, L.S., 1997. Dose-response relationships for polyhalogenated 
      dioxins and dibenzofurans following subchronic treatment in mice. I .CYP1A1 and 
      CYP1A2 enzyme activity in liver, lung and skin. Toxicol. Appl. Pharmacol. 130, 
      197-208; DeVito, M.J., Menache, G., Diliberto, J.J., Ross, D.G., Birnbaum L.S., 
      2000. Dose-response relationships for induction of CYP1A1 and CYP1A2 enzyme 
      activity in liver, lung, and skin in female mice following subchronic exposure to 
      polychlorinated biphenyls. Toxicol. Appl. Pharmacol. 167, 157-172] Female mice 
      received 0, 1.5, 15, 150 or 450 ng TCDD/kg/day or approximately 0, 1.5, 15, 150 
      or 450 ng TEQ/kg/day of MIX-1 or MIX-2 by gavage 5 days per week for 13 weeks. 
      Mice were immunized 3 days after the last exposure and 4 days later, body, 
      spleen, thymus, and liver weights were measured, and antibody response to SRBCs 
      was observed. Exposure to TCDD, MIX-1, and MIX-2 suppressed the antibody response 
      in a dose-dependent manner. Two-way ANOVA indicated no differences in the 
      response between TCDD and the mixtures for body weight, spleen/body weight and 
      decreased antibody responses. The results support the use of the TEF methodology 
      and suggest that immune suppression by dioxin-like chemicals may be of concern at 
      or near background human exposures.
FAU - Smialowicz, R J
AU  - Smialowicz RJ
AD  - Experimental Toxicology Division, National Health, and Environmental Effects, 
      Research Laboratory, US Environmental Protection Agency, Research Triangle Park, 
      North Carolina 27711, USA.
FAU - DeVito, M J
AU  - DeVito MJ
FAU - Williams, W C
AU  - Williams WC
FAU - Birnbaum, L S
AU  - Birnbaum LS
LA  - eng
PT  - Journal Article
DEP - 20071203
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Benzofurans)
RN  - 0 (Dibenzofurans, Polychlorinated)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
SB  - IM
MH  - Animals
MH  - Antibody Formation/drug effects
MH  - Benzofurans/*toxicity
MH  - Body Weight/drug effects
MH  - Cytochrome P-450 CYP1A1/analysis/metabolism
MH  - Cytochrome P-450 CYP1A2/analysis/metabolism
MH  - Dibenzofurans, Polychlorinated
MH  - Dose-Response Relationship, Drug
MH  - Erythrocytes/immunology
MH  - Female
MH  - Immune Tolerance/*drug effects
MH  - Liver/*drug effects/enzymology
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Organ Size/drug effects
MH  - Polychlorinated Biphenyls/*toxicity
MH  - Polychlorinated Dibenzodioxins/*analogs & derivatives/toxicity
MH  - Sheep
EDAT- 2008/01/15 09:00
MHDA- 2008/05/06 09:00
CRDT- 2008/01/15 09:00
PHST- 2007/09/28 00:00 [received]
PHST- 2007/11/15 00:00 [revised]
PHST- 2007/11/19 00:00 [accepted]
PHST- 2008/01/15 09:00 [pubmed]
PHST- 2008/05/06 09:00 [medline]
PHST- 2008/01/15 09:00 [entrez]
AID - S0041-008X(07)00520-0 [pii]
AID - 10.1016/j.taap.2007.11.018 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2008 Mar 15;227(3):477-84. doi: 
      10.1016/j.taap.2007.11.018. Epub 2007 Dec 3.