ABSTRACT
Endocrine disruptors (xenohormones) are exogenous substances or compounds that cause adverse health effects in the organism by disrupting the endocrine functions (1,2,3). Endocrine disruptions mostly occur on the basis of genetic predisposition. Natural or synthetic chemical endocrine disrupting substances that we are surrounded with and are exposed to in the modern world lead to clinical disorders by intervening with hormonal physiology (4). At first, endocrine disruptors were thought to act only via nuclear hormone receptors such as estrogen, androgen, progesterone, thyroid and retinoid receptors. However, recent studies have shown that the mechanism of action of endocrine disruptors is not that simple. Endocrine disruptors are thought to exert effects on endocrine and reproductive systems through nuclear receptors, non-nuclear steroid hormone receptors (membrane estrogen receptors), non-steroid receptors (neurotransmitter receptors such as serotonin, dopamine, norepinephrine receptors), orphan receptors (aryl hydrocarbon receptor), enzymatic path-
ways involving steroid biosynthesis and/or metabolism, and numerous other mechanisms (3). Endocrine disruptors are also known as endocrine modulators, hormone active agents, endocrine active agents, endocrine toxins or xenohormones (5,6). Molecules defined as endocrine disruptors constitute an extremely heterogeneous group and include synthetic chemicals used as industrial solvents/lubricants and their by-products (polychlorinated biphenyls, polybrominated biphenyls, dioxins), plastics (bisphenol A), plasticisers (phthalates), pesticides [methoxychlor, chlorphyrifos, dichlorodiphenyl-trichloroethane (DDT)], fungicides (vinclozolin) and pharmaceutical agents (diethylstilbestrol) (3). Natural chemicals found in human and animal food (phytoestrogens such as genistein, coumestrol) also act as endocrine disruptors (5,7) (Table 1). Different from adults, infants and children are not exposed only to chemical toxins in the environment but may also be exposed indirectly during their intrauterine life. Hundreds of toxic substances may affect the fetus via the placental cord and these substances may be excreted via the meconium. These include countless number of neuro-immune and endocrine toxic chemical components that may influence the critical steps of hormonal, neurological and immunological development. It has been demonstrated in animal and human studies that affected offsprings are not only born with congenital abnormalities but may also suffer from several health and behavioral problems throughout their lifespan (8). Measurement of endocrine disruptor levels in the umbilical cord blood of newborns is one of the several methods to determine intrauterine fetal exposure to chemical substances. In a study conducted in the US by the Environmental Working Group (EWG), 413 toxic substances were sought in the umbilical cord blood of 10 newborns, with positive results for 287 of these substances (Table 2). In the same study, many endocrine-disrupting chemical compounds including pharmaceutical agents, illegal drugs, heavy metals and pesticides were also detected in the meconium samples from the newborns. Children and especially newborns are more sensitive to environmental toxins compared to adults. Metabolic pathways in infants are immature, especially in the first months of life. Newborns differ from adults in their ability to metabolize, detoxify and eliminate many toxins. It has been demonstrated in various studies that newborns are affected from chemical toxins to a greater degree than adults (9). Although
exposures have occurred during fetal life or during the neonatal period, the effect of these exposures may sometimes not be observed for many years. For these reasons, some of the states caused by endocrine disruptors are among examples of adult disease states of fetal origin (10). Owing to the fact that endocrine disruptors have low water solubility and high lipid solubility, they accumulate in fatty tissues. Thus, their longterm effects may be observed in later years.
