Accurate Prediction of the Response of Freshwater Fish to a Mixture of Estrogenic Chemicals

Abstract

Existing environmental risk assessment procedures are limited in their ability to evaluate the combined effects of chemical mixtures. We investigated the implications of this by analyzing the combined effects of a multicomponent mixture of five estrogenic chemicals using vitellogenin induction in male fathead minnows as an end point. The mixture consisted of estradiol, ethynylestradiol, nonylphenol, octylphenol, and bisphenol A. We determined concentration–response curves for each of the chemicals individually. The chemicals were then combined at equipotent concentrations and the mixture tested using fixed-ratio design. The effects of the mixture were compared with those predicted by the model of concentration addition using biomathematical methods, which revealed that there was no deviation between the observed and predicted effects of the mixture. These findings demonstrate that estrogenic chemicals have the capacity to act together in an additive manner and that their combined effects can be accurately predicted by concentration addition. We also explored the potential for mixture effects at low concentrations by exposing the fish to each chemical at one-fifth of its median effective concentration (EC50). Individually, the chemicals did not induce a significant response, although their combined effects were consistent with the predictions of concentration addition. This demonstrates the potential for estrogenic chemicals to act additively at environmentally relevant concentrations. These findings highlight the potential for existing environmental risk assessment procedures to underestimate the hazard posed by mixtures of chemicals that act via a similar mode of action, thereby leading to erroneous conclusions of absence of risk.

Combined effects of estrogenic chemicals with the same mode of action using an estrogen receptor binding bioassay

“…Considering the estrogenic potencies of chemicals varying with species and bioassay endpoint, the potency values obtained from the two-hybrid yeast assay for individual substances were compared with those reported in the literature using other methods. We found that our estrogenic activity order for the test chemicals was close to, and the EC 50 values were slightly lower than most of the published ones (Brian et al, 2005;Correia et al, 2007;Folmar et al, 2002;Liu et al, 2009;Thorpe et al, 2005), which illustrates the reliability and high sensitivity of our yeast strain.…”

Repeating History: Pharmaceuticals in the Environment

“…For example, EE2 and 17-trenbolone, a synthetic steroidal androgen used in livestock, are quite analogous in that they both impact the reproductive endocrine system of fish at very low yet environmentally relevant (nanograms-per-liter) concentrations in the water (8,14,15). However, current testing approaches would consider their ecological risks differently.…”

An overall risk probability-based method for quantification of synergistic and antagonistic effects in health risk assessment for mixtures: theoretical concepts

“…There are evidences that estrogenic compounds act either additively (Brian et al, 2005) or mildly synergistically (Christiansen et al, 2009). If we assume the two EDCs do not interact with each other, the ORP for exposure to the mixture of two is P m = 1 -(1 -0.081) (1 -0.27) = 0.33 Equation (17) On the other hand, if we use a synergistic coefficient of 0.10 to represent the interacting effect of the two, the ORP for exposure to the mixture is 1 -P E2 = (1 -0.081) (1 -0.10 x 0.27) = 0.894 Equation (18a) 1 -P EE2 = (1 -0.27) (1 -0.10 x 0.081) = 0.724 Equation ( …”