Mixture Effects of Estrogenic Pesticides at the Human Estrogen Receptor ? and ?.

ABSTRACT: Consumers of fruits and vegetables are frequently exposed to small amounts of hormonally active pesticides, some of them sharing a common mode of action such as the activation of the human estrogen receptor ? (hER?) or ? (hER?). Therefore, it is of particular importance to evaluate risks emanating from chemical mixtures, in which the individual pesticides are present at human-relevant concentrations, below their corresponding maximum residue levels. Binary and ternary iso-effective mixtures of estrogenic pesticides at effect concentrations eliciting a 1 or 10% effect in the presence or absence of 17?-estradiol were tested experimentally at the hER? in the yeast-based estrogen screen (YES) assay as well as in the human U2-OS cell-based ER? chemical-activated luciferase gene expression (ER? CALUX) assay and at the hER? in the ER? CALUX assay. The outcome was then compared to predictions calculated by means of concentration addition. In most cases, additive effects were observed with the tested combinations in all three test systems, an observation that supports the need to expand the risk assessment of pesticides and consider cumulative risk assessment. An additional testing of mixture effects at the hER? showed that most test substances being active at the hER? could also elicit additive effects at the hER?, but the hER? was less sensitive. In conclusion, effects of the same ligands at the hER? and the hER? could influence the estrogenic outcome under physiological conditions.

SUBMITTER: Seeger B 

PROVIDER: S-EPMC4728068 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature