Studies on Metallocene Polyolefin and Polyvinyl Chloride for Blood ...

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Introduction
blasts, probably subsequent to the synergistic action of plasticizer and stabilizer, while in 1998
Fischer et al. (108) showed a dose-dependent impairment in leukocyte oxidative metabolism in
vitro. More recently, an increase in lipid peroxidation of erythrocytes and consequent hernolysis,
presumably due to oxidative damage to the cell membrane, as well as a decrease in the concentration
ofvitamin E in blood stored in DEHP-plasticized bags have been reported Cl09-111).
The Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental
Protection Agency identified the reproductive toxicity ofDEHP (112).
Colon et al. (2000) reported elevated levels of several phthalates [including diethyl phthalate
(DEP), DBP, and DEHP] in serum samples from young girls with premature breast development
(113).
1.5.1 Effect of DEHP Exposure on Infants
<strong>Studies</strong> on animals have shown that younger developing animals are more vulnerable to testicular
toxicity than the older ones (114-117). It has been indicated that children would absorb
chemicals more efficiently, process them more slowly and eliminate them less efficiently than
adults (118). In another study, Parke showed that neonates were often more receptive than
adults to the toxic effects of chemicals (119). Infants in neonatal intensive care units are regularly
exposed to high doses of DEHP following various medical procedures. Because of their
smaller size, children and especially premature and small infants may receive a larger dose of
DEHP on a milligram per kilogram basis than adults when the same-size medical device is used
for all ages. Therefore, potential exposure risk to DEHP will be presumably higher for infants,
particularly infants at an early and more sensitive stage oftheir development
The toxicokinetics of DEHP are potentially quite different in very young and premature infants.
In mature humans, like in rodents, DEHP is metabolized to MEHP by pancreatic lipase and
absorbed through the gut. It is then glucuronidated and excreted, resulting in little or no tissue
accumulation. In infants, pancreatic lipase systems are not fully mature until 6 to 12 months of
age. (120-122). Neither premature nor full-term infants have mature glucuronidation until about
3 months of age (123). Thus, this important clearance mechanism for MEHP is not fully available
to neonates and young infants, and may lead to slower MEHP excretion and higher levels
ofMEHP in neonates than in older children and adults (124). In infants, DEHP exposure mainly
occurs in Neonate Intensive Care Units (NICU) during treatments. (53,125). Calafat et al
conducted a study to determine whether premature infants who undergo various medical procedures
were at increased risk of exposure to DEHP than the general population (126). This study
provides the first quantitative evidence confirming that newborns who undergo intensive
therapeutic medical interventions are exposed to higher concentrations of DEHP than the
general population. Newborn infants could be exposed to more than 4 mg per kg of DEHP per
day through blood transfusions (46).
FDA has been identified the following groups at greatest risk on DEHP exposure. The greatest
risk groups are newboms including premature newborns, infants and young children, ECMO
patients, cardiopulmonary bypass patients, exchange transfusion infant and children patients,
patients receiving certain IV therapies, particularly those on TPN and those receiving lipophilic
drug formulations. Additional groups possibly at risk include trauma patients receiving multiple