Taiwan Agricultural Chemicals and Toxic Substances Research InstituteTaiwan
Benomyl and its metabolite carbendazim were reported to induce reproductive and developmental toxicity and endocrine-disrupting activity in rats. The exactly underlying mechanism of reproductive and developmental toxicity and endocrine-disrupting activity still remain unclear. Based on our unpublished data it showed that the antiandrogen flutamide can completely recover the reproductive and developmental toxicity including embryolethality induced by benomyl and carbendazim in rats. This manuscript aimed to review and generalize the results based on our previous reports. Androgen receptor might play an important role in benomyl- and carbendazim-induced reproductive and developmental toxicity and endocrine-disrupting activity. The evidences were (1) androgen- and androgen receptor-dependent mechanisms are possibly involved in carbendazim-induced toxicity; (2) carbendazim exposure in utero displays a transient and weak androgenic effect and reduces flutamide antiandrogenicity in male rats; (3) antagonistic effect of flutamide on the carbendazim-androgenic effect on mRNA and protein levels; (4) benomyl and carbendazim exhibit an androgenic effect, leading to increase weight of ventral prostate and seminal vesicles and uterine fluid retention in young adult rats. The molecular underlying mechanism of reproductive and developmental toxicity and endocrine-disrupting activity induced by benomyl and carbendazim through androgen receptor need to be further investigated.
Part of the book: Endocrine Disruptors
Endocrine-disrupting activity induced by xenobiotics might pose a possible health threat. Facing so many chemicals, there is an issue on how we detect them precisely and effectively. The whole embryo culture (WEC) test, an ex vivo exposure lasting 48 hours with rat embryos of 10.5 days old, is used to detect prenatal developmental toxicity. We extended the WEC function to detect the endocrine-disrupting activity induced by environmental chemicals. Results showed that in the development of rat embryo, basically 17ß-estradiol, triiodothyronine, triadimefon, penconazole, and propiconazole exhibited no significant effect on yolk sac circulatory system, allantois, flexion, heart caudal neural tube, hindbrain, midbrain, forebrain, otic system, optic system, olfactory system, maxillary process, forelimb, hind limb, yolk sac diameter, crown-rump length, head length, and developmental score. In the immunohistochemistry, the positive control of 17ß-estradiol showed positive effect for its receptor expressions. These three triazoles induced expressions of ERα and ERß in WEC. This result basically meets the mode of action that triazoles were designed to disrupt the synthesis of steroid hormone. Here we gave a strategy to detect possible endocrine-disrupting activity induced by xenobiotics in food. This strategy is quick to initiate the whole rat embryo culture with 10.5 days to detect the hormone receptors such as androgen, estrogen, thyroid, aromatase activity and its related receptors.
Part of the book: Medicinal Chemistry
Pyrethroid insecticides are suspected endocrine-disrupting chemicals. Deltamethrin has been reported to antagonize thyroid hormone receptor activity in a reporter assay. We hypothesized that deltamethrin alters thyroid function. Male and female rats were administered daily oral gavages with 0, 0.3, 1, or 3 mg/kg/day deltamethrin on postnatal days 23–53 and 22–42, respectively. Results showed that deltamethrin decreased the relative thyroid weight in 0.3 and 1 mg/kg/day in female but not in male rats. Although the histology and several parameters of thyroid were not affected, the decreased relative weight exhibited underlying meaning. Deltamethrin delayed the age of vaginal opening (VO) and increased body weight upon VO in 3 mg/kg/day. Deltamethrin failed to delay the age of preputial separation in male rats. In the respective of serum hormone concentration, deltamethrin increased 17β-estradiol (E2) with dose-dependent manner in female rats. The novel finding is that deltamethrin decreased thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) in the female rats. In contrast, deltamethrin increased T3 and TSH but not in T4 in male rats. We inferred that deltamethrin disrupts thyroid hormone and might be related to estrogen receptor agonist. The future work is to investigate if deltamethrin disrupts the hypothalamus-pituitary-thyroid axis.
Part of the book: Comparative Endocrinology of Animals