In vitro–in vivo correlations for endocrine activity of a mixture of 5 currently used pesticides

Two pesticide mixtures consisting of three and five currently used pesticides, respectively, were investigated for potential endocrine disrupting effects. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin and Mix 5 contained the same 3 pesticides plus malathion and terbuthylazine. All five single pesticides and the two mixtures were tested in vitro in H295R cells for effects on steroidogenesis.

All five pesticides individually and both mixtures affected steroidogenesis. The mixtures caused an increase in progesterone and a decrease in testosterone, and Mix 5 also increased estradiol, indicating increased aromatase activity. The pesticide-mixtures were also investigated in vivo in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses.

All 5 pesticides could be detected in the amniotic fluid, demonstrating exposure of the fetuses. Decreased estradiol and increased T4 levels were seen in dams exposed to Mix 5. Neither of the two mixtures showed any effects on fetal hormone levels, but Mix 5 did caused a significant increase in aromatase mRNA levels in adrenal glands from female fetuses.

Overall, aromatase induction in adrenals was found for Mix 5 both in vitro and in vivo. However, the hormonal responses in vitro were only partly reflected in vivo, probably due to ADME interactions, as the amniotic pesticide levels were negatively affected by the number of compounds present in the mixtures.

Nonetheless, the H295R assay gives hints on interference with steroidogenesis, and it is suggested that one underlying mechanism for these pesticides is disturbance of steroidogenic enzymes.