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

Abstract

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 reported. In the last two decades since this serious public health anomaly has been observed, no explanation for this phenomenon has been found. Some organic pollutants, including pesticides and some plasticizers, can disrupt normal sexual development in wildlife, and many of these have been widely used in Puerto Rico. This investigation was designed to identify pollutants in the serum of Puerto Rican girls with premature thelarche. A method for blood serum analysis was optimized and validated using pesticides and phthalate esters as model compounds of endocrine-disrupting chemicals. Recovery was > 80% for all compounds. We performed final detection by gas chromatography/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were detected in the serum of the study or control subjects. Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.

Di-(2-ethylhexyl) phthalate induces production of inflammatory molecules in human macrophages

“…DEHP, however, has been recognized as a reproductive and developmental toxicant. Phthalates have been reported to be related to the feminization of male infants in the USA [7], and to the early onset of puberty in young girls in Puerto Rico [8]. In men, correlations have been observed between concentrations of thyroid hormone and DEHP metabolites [9].…”

Survey of Levels of Phthalate Ester Plasticizers in a Sewage Lagoon Effluent and a Receiving Stream

“…The Food and Drug Administration (FDA) recently issued a report acknowledging that PCV medical devices may be a concern to some critical ill infants (FDA, 2001). Puerto Rican girls with premature breast development (thelarche) had higher levels of blood phthalates compared to other girls, suggesting an association between phthalate exposure and abnormal reproductive development (Colon et al, 2000).…”

Stoffmonographie Di(2-ethylhexyl)phthalat (DEHP)—Referenzwerte für 5oxo-MEHP und 5OH-MEHP im Urin

“…Eine Stu die von Colón et al [49] gibt wei te re Hin wei se auf die östro ge nen und an ti an dro ge nen Wir kun gen von Phthalsäu rees tern, spe zi ell DEHP, auch für den Men schen. So wei sen Mäd chen aus Puer to Rico, für die eine prä ma ture The larche (vor zei ti ge Knos pung der weib li chen Brust) fest ge stellt wur de, im Mit tel mehr als 6-fach hö he re Kon zen tra tio nen an DEHP im Se rum auf als Mäd chen, die als Kon troll kol lek tiv un ter sucht wur den (450 µg/L vs. 70 µg/L).…”

“…DEHP (und MEHP) be schrei ben Colón et al [49]. Auch die se Au to ren ver set zen das Serum mit Ace to ni tril, ex tra hie ren mit Hex an/Di chlor me than und ver wen den diesen Ex trakt dann ohne wei te re Auf rei nigung, je doch nach Einen gen, für die GC-MS. Mit ei ner ähn li chen Auf ar bei tung aber un ter Ver wen dung von GC-ECD bestimm ten Sjö berg et al [86] die Kon zen tratio nen an DEHP und MEHP im Plas ma Neu ge bo re ner, die eine Blut trans fu si on er hal ten hat ten.…”

“…A: Gaschro ma to gra phie-Mas sen spek trome trie: [49] un ter such ten ne ben Die thyl ph tha lat, Di bu tyl ph tha lat, Ben zylbu tyl ph tha lat und Di-n-oc tyl ph tha lat die DEHP-Kon zent ra ti on im Se rum jun ger Mäd chen aus Pu er to Rico. DEHP war im Se rum der Mäd chen mit prä ma tur er Thelar che in 25 von 41 Fäl len nach weis bar, die Kon zen tra tio nen be tru gen zwi schen "nicht nach weis bar" und 2098 µg/L.…”