Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides.
The present study investigated whether a mixture of low doses of five environmentally relevant endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse developmental toxicity effects in rats. In rat dams, a significant increase in gestation length was seen, while in male offspring increased nipple retention and increased incidence and severity of genital malformations were observed. Severe mixture effects on gestation length, nipple retention and genital malformations were seen at dose levels where the individual pesticides caused no or smaller effects when given alone. Generally, the mixture effect predictions based on dose-additivity were in good agreement with the observed effects. The results indicate that there is a need for modification of risk assessment procedures for pesticides, in order to take account of the mixture effects and cumulative intake, because of the potentially serious impact of mixed exposure on development and reproduction in humans.
National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark. ulha@food.dtu.dk
Ulla
U
Hass
Julie
J
Boberg
Sofie
S
Christiansen
Pernille Rosenskjold
PR
Jacobsen
Anne Marie
AM
Vinggaard
Camilla
C
Taxvig
Mette Erecius
ME
Poulsen
Susan Strange
SS
Herrmann
Bodil Hamborg
BH
Jensen
Annette
A
Petersen
Line Harder
LH
Clemmensen
Marta
M
Axelstad
D000014:Abnormalities, Drug-Induced; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D004347:Drug Interactions; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005837:Genitalia, Male / Q000002:abnormalities / Q000187:drug effects; D006801:Humans; D008297:Male; D008431:Maternal-Fetal Exchange; D015233:Models, Statistical; D010575:Pesticides / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D046468:Sexual Development / Q000187:drug effects*; D013256:Steroids / Q000378:metabolism
D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D010575:Pesticides; D013256:Steroids