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Toxicokinetic of HEMA in guinea pigs
Authors:Reichl F-X  Durner J  Kehe K  Manhart J  Folwaczny M  Kleinsasser N  Hume W R  Hickel R
Affiliation:

a Walther-Straub-Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University of Munich, Nussbaumstr. 26, 80336, Munich, Germany

b Department of Operative/Restorative Dentistry, Periodontology and Pedodontics Ludwig- Maximilians-University of Munich, Goethestr. 70, 80336, Munich, Germany

c Klinisch experimentelle Onkologie; Department of Otolaryngology - Head and Neck Surgery, Ludwig-Maximilians-University, Munich, Germany

d Dental Research Institute, University of California Los Angeles, Los Angeles CA 90095, USA

Abstract:Objective. Unconverted 2-hydroxyethylmethacrylate (HEMA) can be released from dental resin materials and can enter the body in humans. In the present study the uptake, distribution and excretion of 14C-HEMA applied via different routes were examined in vivo in guinea pigs.

Methods. HEMA (0.02 mmol/kg bw labelled with a tracer dose 14C-HEMA 0.3 Bq/g bw) was administered by gastric tube or by subcutaneous injection. Urine, feces, and exhaled carbon dioxide were collected for 24 h after administration. Guinea pigs were killed 24 h after the beginning of the experiment and various organs removed and 14C radioactivity measured.

Results. Low fecal 14C levels (about 2% of the dose) and urinary levels of about 15% after 24 h were noted with either route of administration. Direct measurement of exhaled CO2 showed that about 70% of the dose left the body via the lungs. Two pathways for the metabolism of 14C-HEMA can be described. It is likely that 14C-pyruvate is formed in vivo resulting in the formation of toxic 14C-HEMA intermediates. 14C-HEMA was taken up rapidly from the stomach and small intestine after gastric administration and was widely distributed in the body following administration by each of the routes.

Conclusions. Clearance from most tissues following gastric and intradermal administration was essentially complete within one day. The peak HEMA levels in all tissues examined after 24 h were at least onemillion-fold less than known toxic levels.

Keywords:Toxicokinetic   Uptake   Distribution   Excretion   Clearance   Metabolism   HEMA   Composites   Toxicity   Guinea pig
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