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Veterinary/zoology session

Toxicokinetics of the adrenocorticolytic compound 3-MeSO2-DDE in lactating and suckling Göttingen minipig
Kismul, Haldis - year 5
SzIE, Faculty of Veterinary Science, Department and Clinic of Reproduction; Department of Production Animal Clinical Science, Norwegian School of Veterinary Science, Oslo
Supervisors: Gyula Huszenicza DVM, Erik Ropstad DVM


3-Methylsulfonyl-4,4’-DDE (3-MeSO2-DDE) is a persistent and bioaccumulative metabolite of 4,4’-DDT, formed through biotransformation of 4,4’-DDE and characterized by a high and tissue-specific toxicity in the adrenal cortex in mouse fetuses, suckling pups and adult mice. 3-MeSO2-DDE also targets the human adrenal cortex kept in tissue-culture ex-vivo and human adrenocortical H295R cells in vitro.

The present study was designed to examine the excretion of 3-MeSO2-DDE in milk, and the maternal and neonatal toxicokinetics following a single oral dose to lactating minipigs. Milk, maternal fat, and plasma from five pigs and their suckling offspring were collected at regular intervals during four weeks. At autopsy on day 30 post partum, adrenals, liver and body fat were sampled from mothers and piglets. The levels of 3-MeSO2-DDE were measured by gas chromatography and the toxicokinetics in mothers and offspring were computed.

The levels of 3-MeSO2-DDE in milk were considerably higher than in maternal and offspring plasma throughout the investigation. Based on both fresh weight and fat contents, the 3-MeSO2-DDE plasma levels in the piglets were about three to four times higher than in the mothers. A strong accumulation of 3-MeSO2-DDE was observed in fat tissue, and a moderate accumulation in adrenals and liver of mothers and offspring. The retained tissue levels in the piglets were consistently higher than in the mothers.

It is concluded that suckling offspring were more exposed than their mothers, which were given 3-MeSO2-DDE orally. The results suggest that human risk assessment of the adrenocorticolytic environmental pollutant 3-MeSO2-DDE should be focussed on breast-fed infants.

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