Research

Environmental Health Perspectives - April 2004

Follow-Up Study of Adolescents Exposed to di-2-Ethylhexyl Phthalate (DEHP) as Neonates on Extracorporeal Membrane Oxygenation (ECMO) Support

Khodayar Rais-Bahrami, Suzan Nunez, Mary E. Revenis, Naomi L. C. Luban, and Billie L. Short

online 7 April 2004

Abstract

di-2-ethylhexyl phthalate (DEHP) is used to make polyvinyl chloride (PVC) plastic tubing soft and flexible. Based on animal data, adverse effects of DEHP exposure may include reduced fertility, and sperm production in males and ovarian dysfunction in females. Known treatments that involve high DEHP exposures are blood exchange transfusions, ECMO and cardiovascular surgery. 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 neonatal ECMO survivors to assess their onset of puberty and sexual maturity. Thirteen male and 6 female subjects at age 14-16 years who had undergone ECMO in the neonatal period were evaluated. 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 LH, FSH, testosterone for males and estradiol for females. With the exception of 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 indicates 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, male and female gonadal functions tested were within normal range for age and sex distribution.

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International Journal of Toxicology vol 22 issue 3
May/June (2003) 159-174

Evaluation of Reproductive Development Following Intravenous and Oral Exposure to DEHP in Male Neonatal Rats

Jon N. Cammack,  Randy D. White,  Donovan Gordon,  Jerome Gass,  Lawrence Hecker,  David Conine,  Uma Swamy Bruen,  Mitchell Friedman, Charles Echols,  Tony Y. Yeh,  and Daniel M. Wilson

Abstract

Di-(2-ethylhexyl)phthalate (DEHP) was administered to 3- to 5-day-old male Sprague-Dawley rats by daily intravenous injections of 60, 300, or 600 mg/kg/day or by daily oral gavage of 300 or 600 mg/kg/day for 21 days. Histopathological evaluation and organ weight measurements were performed on some animals after 21 days of dosing (primary group) and later on the recovery group animals that were held without further treatment until sexual maturity at approximately 90 days of age. No effects of any type were observed in animals treated intravenously with 60 mg/kg/day. Testicular changes, consisting of a partial depletion of the germinal epithelium and/or decrease in diameter of seminiferous tubules, were present in all animals of the 300- and 600-mg/kg/day groups after the 21-day dosing period. Testes weight decreased and liver weight increased in these animals. Testes changes were dose-related and generally more severe among animals dosed orally versus intravenously. In the recovery animals, a residual DEHP-induced decrease in seminiferous tubule diameter was present in the testis of several animals dosed orally at 300 and 600 mg/kg/day, but not in animals dosed intravenously. There was no germinal cell depletion or Sertoli cell alteration observed in any dose group at any time. Notably, no effects on sperm count, sperm morphology, or sperm motility were observed at 90 days of age in any of the groups.

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