title: In vitro-in vivo correlations for endocrine activity of a mixture of currently used pesticides.
abstract: Two pesticide mixtures were investigated for potential endocrine activity. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin, and Mix 5 included malathion and terbuthylazine in addition to the three pesticides in Mix 3. All five single pesticides and the two mixtures were investigated for their ability to affect steroidogenesis in vitro in H295R cells. The pesticides alone and both mixtures affected steroidogenesis with both mixtures causing increase in progesterone and decrease in testosterone. For Mix 5 an increase in estradiol was seen as well, indicating increased aromatase activity. The two mixtures were also investigated in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. Decreased estradiol and reduced placental testosterone were seen in dams exposed to Mix 5. Also a significant increase in aromatase mRNA-levels in female adrenal glands was found for Mix5. However, either of the two mixtures showed any effects on fetal hormone levels in plasma or testis, or on anogenital distance. Overall, potential aromatase induction was found for Mix 5 both in vitro and in vivo, but not for Mix 3, an effect likely owed to terbuthylazine in Mix 5. However, the hormonal responses in vitro were only partly reflected in vivo, probably due to some toxicokinetic issues, as the pesticide levels in the amniotic fluid also were found to be negatively affected by the number of compounds present in the mixtures. Nonetheless, the H295R assay gives hints on conceivable interference with steroidogenesis, thus generating hypotheses on in vivo effects.
authors: Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark. Electronic address: camta@food.dtu.dk.
authors: Camilla
authors: C
authors: Taxvig
authors: Niels
authors: N
authors: Hadrup
authors: Julie
authors: J
authors: Boberg
authors: Marta
authors: M
authors: Axelstad
authors: Rossana
authors: R
authors: Bossi
authors: Eva Cecilie
authors: EC
authors: Bonefeld-Jørgensen
authors: Anne Marie
authors: AM
authors: Vinggaard
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000378:metabolism*
chemical_list: D052244:Endocrine Disruptors; D010575:Pesticides; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol
keywords: Aromatase; Females; H295R; Mixtures; Pesticides; Rat