Diethylhexylphthalate extracted by typical newborn lipid emulsions from polyvinylchloride infusion systems causes significant changes in histology of rabbit liver.
BACKGROUND
Looking for a candidate substance inducing hepatobiliary dysfunction under parenteral nutrition (PN) in newborns, we recently discovered that newborn infusions extract large amounts of the plasticizer diethylhexylphthalate (DEHP) from commonly used polyvinylchloride (PVC) infusion lines. This plasticizer is well known to be genotoxic and teratogenic in animals and to cause changes in various organs and enzyme systems even in humans. The aim of this study was to examine the effect of DEHP, extracted in the same way and in the same amount as in newborns, on livers of young rabbits.


METHODS
Prepubertal rabbits received lipid emulsion through central IV lines continuously for 3 weeks either via PVC or polyethylene (PE) infusion systems. Livers were examined after 1 and 3 weeks by light and electron microscopy.


RESULTS
By light microscopy, hydropic degeneration, single-cell necrosis, fibrosis, and bile duct proliferation were observed more in the PVC group. Electron microscopy revealed multiple nuclear changes, clusters and atypical forms of peroxisomes, proliferation of smooth endoplasmic reticulum, increased deposition of lipofuscin, and a mild perisinusoidal fibrosis only in the PVC group. These changes, which are generally regarded as reaction upon a toxic stimulus, could be exclusively attributed to DEHP.


CONCLUSIONS
This investigation proved that DEHP produces toxin-like changes in livers of young rabbits in the same dose, duration, and method of administration as in newborn infants. For this reason, it is likely that DEHP is the substance that causes hepatobiliary dysfunction in newborns under PN. Possible modes of action of DEHP are proposed.
Loff
P D Steffan
PD
Clinic of Pediatric Surgery, University of Marburg, Germany. steffan.loff@web.de
Subotic
Ulrike
U
Oulmi-Kagermann
Jasmina
J
Kränzlin
Bettina
B
Reinecke
Maria-Franziska
MF
Staude
Christiane
C
D000818:Animals; D000831:Animals, Newborn; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005217:Fat Emulsions, Intravenous; D007260:Infusion Pumps; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron; D010289:Parenteral Nutrition, Total / Q000295:instrumentation* / Q000379:methods*; D010968:Plasticizers / Q000633:toxicity*; D011145:Polyvinyls; D011817:Rabbits; D011897:Random Allocation
D005217:Fat Emulsions, Intravenous; D010968:Plasticizers; D011145:Polyvinyls; C003080:poly(vinyl chloride)-poly(vinyl acetate) copolymer; D004051:Diethylhexyl Phthalate