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ToxSci Advance Access published online on May 2, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg107
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received January 30, 2003; accepted March 25, 2003
© 2003 Society of Toxicology

Risk Assessment

A Mixture of Dioxins, Furans and Non-Ortho PCBs Based Upon Consensus Toxic Equivalency Factors Produces Dioxin-Like Reproductive Effects

J.T. Hamm 1, C.-Y. Chen 2, L.S. Birnbaum 3*

1 Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599-7270; National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709
2 Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7400
3 National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709

* To whom correspondence should be addressed. E-mail: Birnbaum.Linda{at}epa.gov.


  Abstract

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 (Birnbaum and DeVito, 1995). Following the work of Gray et al. with TCDD (1997), we exposed time-pregnant dams on gestation day (GD) 15 at doses up to 1.0µg 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 2.0µg TEQ/kg to examine reproductive effects. This dose elicited the responses observed with 1.0 µg 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 (Vandenberg et al., 1998) reasonably predicts the developmental toxicity of this mixture of dioxin-like PHAHs.

Key Words: PHAH, TCDD, TEF, reproductive development .


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