Follow-up study of adolescents exposed to Di Phthalate as neonates on extracorporeal membrane oxygenation support

Environmental Health Perspectives, Sept, 2004 by Khodayar Rais-Bahrami, Susan Nunez, Mary E. Revenis, Naomi L.C. Luban, Billie L. Short

Results

Except for one female participant with a diagnosis of Marfan syndrome, the rest had normal growth percentiles for age and sex. All the participants had normal laboratory values for thyroid, liver, and renal functions. The levels of LH, FSH, testosterone in males, and estradiol in females were normal and appropriate for the degree of pubertal development. Results of the sex hormones related to pubertal maturation are shown in Tables 1 and 2 as mean values (normal ranges).

Discussion

Our study did not show long-term adverse outcome related to physical growth and pubertal development in adolescents previously exposed to DEHP in the neonatal period. This is in contrast to the animal data in multiple species, which show a variety of reproductive and developmental toxicities when this plasticizer is administered both orally and parenterally.

Individuals who have among the highest exposures to DEHP are those undergoing medical treatments or procedures such as dialysis, exchange transfusion, ECMO, and cardiovascular surgery. Shneider et al. (1989) have shown that babies undergoing ECMO, in which the blood is circulating through PVC tubing, are exposed to 42-140 mg DEHP/kg body weight over a treatment period of 3-10 days (Shneider et al. 1989). Katie et al. (1997) reported a lower level of exposure that ranged from nondetectable to 34.9 mg/kg/treatment period. The nondetectable level resulted from the use of a heparin coating on the DEHP-plasticized PVC circuit. In addition to the heparin coated tubing, Katie et al. (1997) attributed the difference between their study and that of Shneider et al. (1989) to the smaller surface area of the newer ECMO configurations and the varying percentage of DEHP composition in each type of tubing.

Although intravenous exposure to DEHP through the ECMO circuit or other intravenous routes exceeds recommended oral exposure limits, it is difficult to directly compare the two because one is an assumed lifetime daily oral exposure and the other an acute temporary exposure during ECMO therapy. Also, the routes of exposure differ: oral versus intravenous (Doull et al. 1999). Because the human exposure can be similar to the doses that are toxic in rodents, there is an ongoing concern that exposure to DEHP in neonatal intensive care units may adversely affect the developing reproductive organs in these infants (Huber et al. 1996). The most sensitive system appears to be the immature male reproductive tract, especially the Sertoli cell (Parks et al. 2000; Poon et al. 1997).

When DEHP enters the human body, the compound is metabolized into various substances that are more rapidly excreted. The most important of these metabolites, monoethylhexyl phthalate (MEHP) is thought to be responsible for much of DEHP's toxicity. The enzymes that break down DEHP into MEHP are found mainly in the intestines but also occur in the liver, kidney, lungs, pancreas, and plasma. Because conversion of DEHP to MEHP occurs primarily in the intestinal tract, exposure to DEHP by ingestion may be more hazardous than by intravenous exposure, which largely bypasses the intestinal tract (Huber et al. 1996; Lewandowski et al. 1980; Thomas et al. 1979).