Follow-Up Study of Adolescents Exposed to Di(2-Ethylhexyl)
Follow-Up Study of Adolescents Exposed to Di(2-Ethylhexyl)
Di(2-ethylhexyl) phthalate (DEHP) is used to make polyvinyl chloride (PVC) plastic tubing soft and flexible. Animal data show that adverse effects of DEHP exposure may include reduced fertility, reduced sperm production in males, and ovarian dysfunction in females. Known treatments that involve high DEHP exposures are blood exchange transfusions, extracorporeal membrane oxygenation (ECMO), and cardiovascular surgery. Although potential exposure to DEHP in ECMO patients is significant, the exposure has not been associated with short-term toxicity. To evaluate long-term toxicity, we undertook a study of neonatal ECMO survivors to assess their onset of puberty and sexual maturity. We evaluated 13 male and 6 female subjects at 14-16 years of age who had undergone ECMO as neonates. All subjects had a complete physical examination including measurements for height, weight, head circumference, and pubertal assessment by Tanner staging. The testicular volume and the phallic length were measured in male participants. Laboratory tests included thyroid, liver, and renal function as well as measurements of luteinizing hormone, follicle-stimulating hormone, testosterone for males, and estradiol for females. Except for one patient with Marfan syndrome, the rest had normal growth percentile for age and sex. All had normal values for thyroid, liver, and renal functions. Sexual hormones were appropriate for the stage of pubertal maturity. Our results indicate that adolescents exposed to significant quantities of DEHP as neonates showed no significant adverse effects on their physical growth and pubertal maturity. Thyroid, liver, renal, and male and female gonadal functions tested were within normal range for age and sex distribution.
Human exposure to di(2-ethylhexyl) phthalate (DEHP) occurs throughout life. Of particular concern is the exposure of fetuses, preterm infants, and babies because the developing human reproductive system may be affected when the metabolic pathways of detoxification are immature. DEHP has been shown to damage the male and female reproductive systems in newborn animals. Animal studies have shown DEHP to be particularly harmful to developing fetuses: Adverse effects in the reproductive system include changes in the testes, specifically the Sertoli cell, leading to reduced fertility and changes in sperm production in males (Foster et al. 2001; Park et al. 2002; Poon et al. 1997) and ovarian dysfunction and decreased hormone production in females (Davis et al. 1994; Lovekamp-Swan and Davis 2003). Respiratory distress and changes in kidney and liver function have also been linked to DEHP exposure (Crocker et al. 1988; Kevy and Jacobson 1982; Latini 2000; Rock et al. 1987; Roth et al. 1988; Ward et al. 1998).
DEHP derives from a family of chemicals called phthalates. These chemicals are used to make polyvinyl chloride (PVC) plastic tubing soft and flexible. Because DEHP does not bind to the plastic, it can leach out of the PVC products. DEHP is widely used in PVC disposable medical devices. As in other products, DEHP can leach out of flexible PVC medical devices into the solution or medication it contains and subsequently into the patient (Rubin and Schiffer 1976).
Species differences in toxicity and metabolism of DEHP have created considerable debate about the relevance of studies in rodents to human health. However, exposures in neonatal intensive care units (NICUs) are potentially at or above levels known to cause adverse health effects in relevant animal studies (e.g., Tickner et al. 2001). For infants requiring intensive care, DEHP exposure can occur at three orders of magnitude greater than average adult exposures and at or above levels shown to cause adverse reproductive effects in animals (e.g., Tickner et al. 2001).
DEHP concentrations in blood and blood products are of particular concern for neonates who receive regular blood transfusions. The most commonly used blood products--packed red blood cells and plasma--are typically stored in DEHP plasticized bags and administered to patients through DEHP plasticized intravenous tubes. Less common treatments that involve potentially high DEHP exposures are blood exchange transfusions and extracorporeal membrane oxygenation (ECMO). Although potential exposure to DEHP in ECMO patients is significant, it has not been associated with short-term toxicity. To evaluate long-term toxicity, we undertook a study of adolescents who had previously undergone ECMO treatment in the neonatal period to assess their onset of puberty and sexual maturation in comparison to an age- and sexmatched reference population.
Di(2-ethylhexyl) phthalate (DEHP) is used to make polyvinyl chloride (PVC) plastic tubing soft and flexible. Animal data show that adverse effects of DEHP exposure may include reduced fertility, reduced sperm production in males, and ovarian dysfunction in females. Known treatments that involve high DEHP exposures are blood exchange transfusions, extracorporeal membrane oxygenation (ECMO), and cardiovascular surgery. Although potential exposure to DEHP in ECMO patients is significant, the exposure has not been associated with short-term toxicity. To evaluate long-term toxicity, we undertook a study of neonatal ECMO survivors to assess their onset of puberty and sexual maturity. We evaluated 13 male and 6 female subjects at 14-16 years of age who had undergone ECMO as neonates. All subjects had a complete physical examination including measurements for height, weight, head circumference, and pubertal assessment by Tanner staging. The testicular volume and the phallic length were measured in male participants. Laboratory tests included thyroid, liver, and renal function as well as measurements of luteinizing hormone, follicle-stimulating hormone, testosterone for males, and estradiol for females. Except for one patient with Marfan syndrome, the rest had normal growth percentile for age and sex. All had normal values for thyroid, liver, and renal functions. Sexual hormones were appropriate for the stage of pubertal maturity. Our results indicate that adolescents exposed to significant quantities of DEHP as neonates showed no significant adverse effects on their physical growth and pubertal maturity. Thyroid, liver, renal, and male and female gonadal functions tested were within normal range for age and sex distribution.
Human exposure to di(2-ethylhexyl) phthalate (DEHP) occurs throughout life. Of particular concern is the exposure of fetuses, preterm infants, and babies because the developing human reproductive system may be affected when the metabolic pathways of detoxification are immature. DEHP has been shown to damage the male and female reproductive systems in newborn animals. Animal studies have shown DEHP to be particularly harmful to developing fetuses: Adverse effects in the reproductive system include changes in the testes, specifically the Sertoli cell, leading to reduced fertility and changes in sperm production in males (Foster et al. 2001; Park et al. 2002; Poon et al. 1997) and ovarian dysfunction and decreased hormone production in females (Davis et al. 1994; Lovekamp-Swan and Davis 2003). Respiratory distress and changes in kidney and liver function have also been linked to DEHP exposure (Crocker et al. 1988; Kevy and Jacobson 1982; Latini 2000; Rock et al. 1987; Roth et al. 1988; Ward et al. 1998).
DEHP derives from a family of chemicals called phthalates. These chemicals are used to make polyvinyl chloride (PVC) plastic tubing soft and flexible. Because DEHP does not bind to the plastic, it can leach out of the PVC products. DEHP is widely used in PVC disposable medical devices. As in other products, DEHP can leach out of flexible PVC medical devices into the solution or medication it contains and subsequently into the patient (Rubin and Schiffer 1976).
Species differences in toxicity and metabolism of DEHP have created considerable debate about the relevance of studies in rodents to human health. However, exposures in neonatal intensive care units (NICUs) are potentially at or above levels known to cause adverse health effects in relevant animal studies (e.g., Tickner et al. 2001). For infants requiring intensive care, DEHP exposure can occur at three orders of magnitude greater than average adult exposures and at or above levels shown to cause adverse reproductive effects in animals (e.g., Tickner et al. 2001).
DEHP concentrations in blood and blood products are of particular concern for neonates who receive regular blood transfusions. The most commonly used blood products--packed red blood cells and plasma--are typically stored in DEHP plasticized bags and administered to patients through DEHP plasticized intravenous tubes. Less common treatments that involve potentially high DEHP exposures are blood exchange transfusions and extracorporeal membrane oxygenation (ECMO). Although potential exposure to DEHP in ECMO patients is significant, it has not been associated with short-term toxicity. To evaluate long-term toxicity, we undertook a study of adolescents who had previously undergone ECMO treatment in the neonatal period to assess their onset of puberty and sexual maturation in comparison to an age- and sexmatched reference population.
Source...