Defining the Impact of Weakly Estrogenic Chemicals on the Action of Steroidal Estrogens

Abstract

We tested whether bisphenol A (BPA) or o,p'-DDT, when combined with 17beta-estradiol (E2), would contribute to the overall mixture effect using a yeast reporter gene assay, the yeast estrogen screen. Following comprehensive concentration-response analyses of the single agents, the pharmacologically well-founded models of concentration addition and independent action were used to predict entire concentration-response relationships for mixtures of the agents with a variety of fixed mixture ratios, assuming additivity. For molar mixture ratios proportional to the levels normally found in human tissues (i.e., below 1:5000, E2:BPA or o,p'-DDT), these predictions suggest that the effects of individual xenoestrogens are too weak to create an impact on the actions of steroidal hormones. However, at mixture ratios more in favor of the xenoestrogens, a significant contribution to the overall mixture effect was predicted. The predictions were tested experimentally. The observed combined effects of mixtures of E2 with either BPA or o,p'-DDT did not deviate from the additivity expectation. On combining E2 with either BPA or o,p'-DDT at approximately equieffective concentrations corresponding to molar mixture ratios between 1:20,000 and 1:100,000 (E2:BPA or o,p'-DDT), substantial modulations of the effects of E2 became discernible. The assumption that weak xenoestrogens are generally unable to create an impact upon the already strong effects of endogenous steroidal estrogens is not supported by our observations. Our studies indicate that the potential health implication of additive combination effects between xenoestrogens and steroidal estrogens deserve serious consideration.

Monofluorinated Analogues of Polybrominated Diphenyl Ethers as Analytical Standards: Synthesis, NMR, and GC-MS Characterization and Molecular Orbital Studies

“…For the quantification of responses, however, one should be extra cautious for the presence of partial and/or superagonistic estrogens. This study confirms the suitability of CA to describe the effects of mixtures of similar acting xeno-estrogens in reporter gene assays as reported earlier (3,12,17,18).…”

Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action.

“…In a recent study of mixtures of estradiol and the weak xenoestrogens bisphenol A and o,p´-DDT (Rajapakse et al 2001), we found that both the hormone and the xenoestrogens contributed in equal measure to the observed combination effects when combined at concentrations that produced similar responses. Furthermore, model calculations carried out by our group suggested that combinations of a large number of xenoestrogens might modulate the effects of 17β-estradiol, even when each individual xenoestrogen is present at concentrations that alone would not produce measurable effects (Kortenkamp and Altenburger 1999).…”

“…We followed a protocol developed by Routledge and Sumpter (1996) exactly as described by Rajapakse et al (2001). We obtained singleagent data from at least three experiments run in duplicate, and mixture samples were run in duplicate on at least two separate occasions.…”

“…To meet these requirements, we used the yeast estrogen screen (YES) (Routledge and Sumpter 1996), which has proven to yield highly reproducible results (Payne et al 2000;Rajapakse et al 2001). …”

Avaliação ecotoxicológica do fármaco cloridrato de fluoxetina e do surfactante dodecil sulfato de sódio quando submetidos a tratamento por radiação ionizante

“…Essa avaliação pode depender de alguns fatores, tais como, potência dos componentes da mistura, a relação resposta-concentração (razão de mistura) de uma substância em uma mistura, como também de efeitos como sinergismo e antagonismo que podem desviar os efeitos esperados (Rajapakse et al, 2001;Silva et al, 2002;Jonsson & Aoyama, 2007 (Bautitz, 2010;Borrely, 2001;Haag & Yao, 1992;Buxton et al, 1988).…”