EDCs in Singapore seawaters: mixtures may multiply effects.

A number of chemicals that end up in the waste stream--pesticides, some polychlorinated biphenyls, dioxins, synthetic steroids, and excreted drugs--can disrupt hormone signaling in vertebrates. These endocrine-disrupting compounds (EDCs) can interfere with both androgens and estrogens, which are responsible for the development of male and female sex characteristics, respectively. This month, Yinhan Gong and colleagues at the National University of Singapore report that enclosed marine waters near industrial areas can contain high concentrations of EDCs [EHP 111:1448-1453]. In addition, complex mixtures of compounds in these waters can dramatically amplify the effects of androgens and estrogens in human cells.

Gong and colleagues collected seawater samples from 21 locations off the Singapore coast near industrial sites such as shipyards and petrochemical plants. Samples were collected from enclosed areas with little tidal action to disperse pollutants as well as from areas with greater tidal flow.

In their experiment, the researchers used human cell lines expressing the androgen receptor (AR) and the two estrogen receptors (ER-[alpha], which is expressed primarily in reproductive tissues such as the breast and uterus, and ER-[beta], which is found in other parts of the body, including, the cardiovascular and nervous systems). They exposed the cell lines to several different types of samples: (1) seawater extracts from each sampling area, (2) extracts from each area in combination with dihydrotestosterone (DHT), an androgen with many of the same effects as testosterone, (3) extracts from each area in combination with 17[beta]-estradiol ([E.sub.2]), the primary form of estrogen produced by vertebrates, (4) DHT alone, and (5) [E.sub.2] alone. As controls, cells were exposed to ultrapure water and tap water from the Singapore water system.

All of the seawater extracts caused some EDC activity in the cell lines. Samples derived from enclosed waters caused the greatest activity; the researchers calculate that in the open waters, the activity would be the equivalent of up to 3% of the AR activity, caused by DHT alone. When the cells were exposed under similar assay conditions to the extracts from enclosed waters in combination with DHT, AR activity increased to 200-900% of that caused by DHT alone, an interaction the researchers call an "exaggerated additive effect."

Results were similar for ER-[alpha]. Samples derived from enclosed waters stimulated ER-[alpha] activity by the equivalent of up to 7% of that caused by [E.sub.2] alone, but activity increased ninefold in cells that were exposed to the extracts in combination with [E.sub.2]. Samples from more open waters did not cause this exaggerated additive effect. None of the seawater samples caused a significant increase in the activity of ER-[beta] receptors, either alone or in combination with [E.sub.2].

The authors conclude that the combined, holistic effects of EDCs in complex marine environments may be strikingly different from what can be predicted from the constituent compounds. Because many vertebrates and some shellfish respond to the same hormones, compounds that disrupt hormone signals in marine fish and shellfish may do the same in humans. According to the researchers, the levels of hormone activity generated by the waters off Singapore may be high enough to affect hormone signaling in marine life, especially after prolonged exposure or bioaccumulation in the food chain. For example, the highest levels of ER-[alpha]. activity calculated for raw seawater were in the range of the sera of women in mid-menstrual cycle. These results may also have implications for human health, because the waters off Singapore are used for seafood farming and recreation, and have been considered as sites for desalination plants.