PMID- 12730615
OWN - NLM
STAT- MEDLINE
DCOM- 20040302
LR  - 20200403
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 74
IP  - 1
DP  - 2003 Jul
TI  - A mixture of dioxins, furans, and non-ortho PCBs based upon consensus toxic 
      equivalency factors produces dioxin-like reproductive effects.
PG  - 182-91
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin) and related polyhalogenated 
      aromatic hydrocarbons (PHAHs) alter the reproductive development of laboratory 
      animals. Therefore, we exposed animals to a mixture of dioxins, furans, and 
      polychlorinated biphenyls (PCBs) that included 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), octachlorodibenzofuran (OCDF), 
      3,3',4,4'-tetrachlorobiphenyl (PCB77), 3,3',4,4',5-pentachlorobiphenyl (PCB126), 
      and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB169). The mixture composition 
      approximated the relative abundance of these compounds in foodstuff (L. S. 
      Birnbaum and M. J. DeVito, 1995, Toxicology Vol. 105, pp. 391-401). Following the 
      work of Gray et al. with TCDD (1997, Toxicology and Applied Pharmacology Vol. 
      146, pp. 11-20), we exposed time-pregnant dams on gestation day (GD) 15 at doses 
      up to 1.0 microgram TCDD toxic equivalency (TEQ)/kg and the development of 
      offspring was monitored. This mixture significantly increased the time to puberty 
      in both male and female offspring. At postnatal day (PND) 32 seminal vesicle 
      weights were decreased; however, only ventral prostate weight was affected at PND 
      49 and no effects were seen at PND 63. In female offspring, the mixture caused 
      dose-dependent increases in the incidence of vaginal thread. 
      Ethoxyresorufin-O-deethylase (EROD) activity was higher than with TCDD the 
      comparable TEQ exposure. Based on the slightly lowered responsiveness to the 
      mixture, we used 2.0 microgram TEQ/kg to examine reproductive effects. This dose 
      elicited the responses observed with 1.0 microgram TCDD/kg. Results indicate that 
      the mixture causes a similar spectrum of effects seen with TCDD and the slightly 
      lowered degree of response based on administered dose appears to be due to 
      decreased transfer of mixture components to the offspring. Thus, the use of the 
      WHO consensus TEFs (M. Van den Berg et al., 1998, Environ. Health Perspec. 106, 
      775-792) reasonably predicts the developmental toxicity of this mixture of 
      dioxin-like PHAHs.
FAU - Hamm, J T
AU  - Hamm JT
AD  - Curriculum in Toxicology, University of North Carolina, Chapel Hill, North 
      Carolina 27599-7270, USA.
FAU - Chen, C-Y
AU  - Chen CY
FAU - Birnbaum, L S
AU  - Birnbaum LS
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20030502
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Dioxins)
RN  - 0 (Furans)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Abnormalities, Drug-Induced/pathology
MH  - Animals
MH  - Birth Weight/drug effects
MH  - Body Weight/drug effects
MH  - Cytochrome P-450 CYP1A1/biosynthesis/genetics
MH  - Dioxins/pharmacokinetics/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Furans/pharmacokinetics/*toxicity
MH  - Genitalia, Male/drug effects/growth & development
MH  - Litter Size/drug effects
MH  - Male
MH  - Microsomes, Liver/drug effects/enzymology
MH  - Organ Size/drug effects
MH  - Placenta/drug effects/enzymology
MH  - Polychlorinated Biphenyls/pharmacokinetics/*toxicity
MH  - Pregnancy
MH  - Rats
MH  - Rats, Long-Evans
MH  - Reproduction/*drug effects
MH  - Sex Characteristics
MH  - Sexual Maturation/drug effects
MH  - Sperm Count
MH  - Tissue Distribution
PMC - PMC7107275
EDAT- 2003/05/06 05:00
MHDA- 2004/03/03 05:00
PMCR- 2020/03/31
CRDT- 2003/05/06 05:00
PHST- 2003/05/06 05:00 [pubmed]
PHST- 2004/03/03 05:00 [medline]
PHST- 2003/05/06 05:00 [entrez]
PHST- 2020/03/31 00:00 [pmc-release]
AID - kfg107 [pii]
AID - 10.1093/toxsci/kfg107 [doi]
PST - ppublish
SO  - Toxicol Sci. 2003 Jul;74(1):182-91. doi: 10.1093/toxsci/kfg107. Epub 2003 May 2.