Estrogenlc activities of chlorinated hydrocarbons

Abstract

Some DDT analogs are estrogenic, particularly o,p'-DDT, which comprises approximately 15-20% of the commercial DDT mixture. Whether this compound or its metabolites are active has not been established. In fact, the data obtained thus far are more confusing than enlightening. For example, CCl4 pretreatment of immature female rats has been reported to inhibit or enhance estrogenic activity of o,p'-DDT, and SKF-525A pretreatment has been reported to enhance or not alter the estrogenic effect. Although o,p'-DDT inhibits binding of estradiol to the estrogen receptor from rat or human at low levels (approximately 1-10 micrometer) in vitro, higher levels are required to inhibit nuclear binding of [3H] estradiol in incubated whole uteri. Futhermore, o,p'-DDT appears to be neither estrogenic nor antiestrogenic in an in vitro estrogen assay. Methoxychlor appears to be "activated" by metabolism, and it is probable that phenolic metabolites are responsible for its estrogenic activity. Since chlorinated hydrocarbons often enhance the metabolism of steroids and may reduce circulating levels of steroids, interactions of the exogenous hormonally active agents with steroid receptors may be self-potentiating in vivo.

Environmental Endocrine Disruption: An Effects Assessment and Analysis

“…Investigators began expressing their concern for estrogenic effects of environmental xenobiotic chemicals more than 25 years ago (3)(4)(5)(6)(7)(8)(9). Within the past 5 years, this concern has become focused and intensified (1,2,(10)(11)(12)(13)(14).…”

Rapid Screening of Environmental Chemicals for Estrogen Receptor Binding Capacity

“…While this relationship between isomer and ER affinity is the same as found by others using MCF-7 or mouse ER (61,63), both isomers display higher affinity for the ER in the FP binding assay (Table 1). In the case of the estrogenic pesticide methoxychlor (12,25), this parent compound was found to have a much lower hrER-a RBA using the FP assay than its estrogenic metabolite HPTE. Furthermore, these ER binding values for methoxychlor and HPTE correspond closely to previous determinations (43,63,64).…”

“…Even though there are few, but significant, examples of a direct link from exposure to an EDC to adverse effects in humans (8)(9)(10), many of the mechanistic pathways mediating the deleterious effects resulting from EDC exposure ofwildlife and laboratory animals have been elucidated (1,(11)(12)(13)(14)(15). As a result, screening for endocrine activity has recently been mandated-in the United States by the Food Quality Protection Act (Public Law 104-170) and the Safe Drinking Water Act amendments (Public Law 104-182) of 1996.…”

Using Three-Dimensional Quantitative Structure-Activity Relationships to Examine Estrogen Receptor Binding Affinities of Polychlorinated Hydroxybiphenyls

“…This approach could be particularly useful when applied to additional hydroxylated and halogenated metabolites or transformation products of certain phenyl-substituted chemicals of environmental concern (32). As previously reported (33) and supported here, the phenolic ring moiety is not a necessary requirement for estrogen receptor affinity. Further binding studies, ideally on the nonhydroxylated PCBs predicted in this report, are needed to assess the unique role and contribution of the hydroxyl group.…”