Triazole fungicides associated with a range of reported male reproductive effects in experimental animals were selected to assess potential toxic modes of action. Wistar Han rats were fed
myclobutanil (M: 100, 500, or 2000 ppm),
propiconazole (P: 100, 500, or 2500 ppm), or
triadimefon (T: 100, 500, or 1800 ppm) from gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0, body and organ weights, serum
hormone levels, age at preputial separation (PPS), sperm morphology and motility, and fertility and fecundity. AGD was increased by the high dose of all three
triazoles, indicating hypervirilization.
Triadimefon delayed PPS, consistent with
delayed puberty, at 1800 ppm. Relative liver weights were increased at PND1, 50, and 92 by all three
triazoles. Hepatocellular
hypertrophy was present at PND50 from
propiconazole and
triadimefon and at PND92 from all three high-dose
triazole treatments. Relative pituitary weights were decreased at PND92 by middle- and high-dose
myclobutanil treatment. Absolute testis weights were increased at PND1 by
myclobutanil, at PND22 by
myclobutanil and
triadimefon, and at PND50 by
propiconazole and
triadimefon treatment. Relative ventral prostate weights were increased at PND92 by
myclobutanil and
triadimefon treatment. Serum
testosterone was increased at PND50 by
triadimefon and at PND92/99 by all three
triazole treatments. Insemination and fertility were impaired by
myclobutanil and
triadimefon treatment. In addition to the reproductive system effects, total serum
thyroxine levels were decreased at PND92 by high-dose
triadimefon. These reproductive effects are consistent with the disruption of
testosterone homeostasis as a key event in the mode of action for
triazole-induced reproductive toxicity.