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A MIXTURE OF DIOXINS, FURANS, AND NON-ORTHO PCBS BASED UPON CONCENSUS TOXIC EQUIVLENCY FACTORS PRODUCES DIOXIN-LIKE REPRODUCTIVE EFFECTS
Citation:
Hamm, J. T., C. Chen, AND L S. Birnbaum. A MIXTURE OF DIOXINS, FURANS, AND NON-ORTHO PCBS BASED UPON CONCENSUS TOXIC EQUIVLENCY FACTORS PRODUCES DIOXIN-LIKE REPRODUCTIVE EFFECTS. TOXICOLOGICAL SCIENCES 74(1):182-191, (2003).
Description:
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 dioxin and dioxin-like compounds including TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 2,3,7,8-tetrachlorodibenzo-p-furan (TCDF), 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), 1,2,3,4,5,6,7,8-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 15 at doses up to 1.0 mg 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 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 the comparable TEQ exposure. Based on the slightly lowered responsiveness to the mixture, we used 2.0g TEQ /kg to examine reproductive effects. This dose elicited the responses observed with 1.0g TCDD /kg. Results indicate that the mixture causes the same 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 after the acute exposure. Thus, the use of the WHO consensus TEFs reasonably predicts the developmental toxicity of a mixture of dioxin-like PHAHs.
Key Words: PHAH; TCDD; TEF; reproductive development