Observations of specific interactions of the heavy metal cadmium with the estrogen receptor have spawned a series of studies to investigate the propensity of this and other heavy metals to act as estrogen mimicks. There is good evidence that Cd has the ability to produce estrogenic effects in rodents, including proliferation of the uterine and mammary tissues. These effects could be suppressed by cotreatment with specific estrogen receptor antagonists, suggesting mediation via the estrogen receptor. Epidemiological studies have provided some support for the idea that Cd poses cancer risks for hormone sensitive tissues, such as the breast and the endometrium. Strikingly, attempts to demonstrate estrogenic effects of Cd in in vitro assay systems have produced mixed results. Mitogenic effects on estrogen receptor-competent cells, activation of estrogen receptor-dependent gene transcription and signalling events associated with the estrogen receptor were observed in cellular models, but could not be reproduced by others. Despite these inconsistencies, the available evidence forces the conclusion that Cd and certain other heavy metals should be regarded as estrogen mimicks. In the context of deterministic risk assessment, this should lend further support for risk reduction measures by controlling exposure to Cd. However, data suitable for the quantitation of estrogenic risks, especially in comparison with the established health risks of Cd, are not yet available. It is recommended to close this knowledge gap with urgency.
