Dioxins/TCDD endocrine disruption

Successful reproduction (and sex) involves many complex chemical processes that can be disrupted at various points to reduce fertility and conception. Part of this process is under control of the endocrine system, and chemicals that affect the endocrine system are termed endocrine disruptors. In the 1950s, understanding of the endocrine system led to the development of birth control pills as a way to reduce fertility in humans. This is a desirable and planned use of endocrine disruptors. Subsequently, it was discovered that a number of chemicals released into the environment could disrupt the endocrine system and reduce fertility of wildlife. Some are concerned that exposure to these chemicals, such as DDT and dioxin (TCDD), may also affect human fertility (Table 17.1). Approximately 15% of couples of reproductive age are infertile. Endocrine disruptors may also affect fetal development, causing demasculization and feminization of the offspring, which in turn cause reduced fertility in the next generation. 

Fig. 9. Relationship between the steady-state bioconcentration factors on a lipid basis (BCFl) of chemicals in different fish species and the n-octanol/water partition coefficient (Kqw) (log/log scale). ( ) Solid circles are chemicals with known endocrine-disrupting properties. Abbreviations of the chemicals p,p -DDT 2,2-bis-(p-chlorophenyl)-l,l,l-trichloroethane. OCDD octachlorodibenzo-p-dioxin. TCDD tetrachlorodibenzo-p-dioxin. HCB hexachloro-benzene. PCA pentachloroanisole. PeCB pentachlorobenzene. MX musk xylene. TeCB tetrachlorobenzene. NP nonylphenol. TCB tetrachlorobenzene. y-HCH y-hexachlorocyclo-hexane (Lindane). PCP pentachlorophenol. DCB dichlorobenzene. BPA bisphenol-A. PCBs polychlorinated biphenyls...

TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin, all of which were shown to be effective blockers of ovulation in this assay (Gao et al. 1999, 2000). The mixture was administered at TCDD-TFQ doses ranging from 0.0038 to 0.0303 mg/kg. Parallel dose-response relationships for inhibition of ovulation were found for the individual agents and for the equipotent mixture. This finding is consistent with the hypothesis that the agents in the tested mixture are likely to block ovulation by additive joint action in a similar mechanism and supports the use of the TEF approach for this type of endocrine disruption. Another PCB congener, 2,2, 4,4 -tetraCB (which has no detectable Ah receptor agonist activity), was inactive at the dose examined in this assay (41.9 mg/kg). The effect of its presence in a mixture with effective components, however, was not studied (Gao et al. 2000). 

Safe SH. 1999. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related environmental antiestrogens Characterization and mechanism of action. In Naz RK, ed. Endocrine disrupters effects on male and female reproductive systems. Boca Raton, FL CRC Press, 187-221. 

Dioxins are released in the environment in emissions from the incineration of mimicipal refuse and certain chemical wastes and in exhaust from automobiles powered by leaded gasohne. Dioxins are highly persistent and accumulate in the environment. They are highly toxic and exhibit endocrine-disrupting activity. Therefore, they are regulated by authorities, e.g., in the United States for the most toxic 2,3,7,8-TCDD the maximum allowed concentration in drinking water is 10 ngmL [21]. 

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