Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development

Premature breast development (thelarche) is the growth of mammary tissue in girls younger than 8 years of age without other manifestations of puberty. Puerto Rico has the highest known incidence of premature thelarche ever re ported. In the last two decades since this serious public health anomaly ha s been observed, no explanation for this phenomenon has been found. Some or ganic pollutants, including pesticides and some plasticizers, can disrupt n ormal sexual development in wildlife, and many of these have been widely us ed in Puerto Rico. This investigation was designed to identify pollutants i n the serum of Puerto Rican girls with premature thelarche. A method for bl ood serum analysis was optimized and validated using pesticides and phthala te esters as model compounds of endocrine-disrupting chemicals. Recovery wa s > 80% for all compounds. We performed final detection by gas chromatograp hy/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were det ected in the serum of the study or control subjects. Significantly high lev els of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and i ts major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68 %) samples from thelarche patients. Of the control samples analyzed, only o ne showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study sugg ests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.