Reproductive toxicity and thyroid effects in Sprague Dawley rats exposed to low doses of ethylenethiourea

• Published in: Food and chemical toxicology 2013-09, Vol.59, p.261-271
• Main Authors: Maranghi, Francesca, De Angelis, Simona, Tassinari, Roberta, Chiarotti, Flavia, Lorenzetti, Stefano, Moracci, Gabriele, Marcoccia, Daniele, Gilardi, Enzo, Di Virgilio, Antonio, Eusepi, Agostino, Mantovani, Alberto, Olivieri, Antonella
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological and medical sciences; biomarkers; Biomarkers - blood; Biomarkers - metabolism; biosynthesis; Congenital Hypothyroidism - chemically induced; Congenital Hypothyroidism - physiopathology; developmental stages; Dose-Response Relationship, Drug; Endocrine Disruptors - administration & dosage; Endocrine Disruptors - toxicity; Estradiol Congeners - blood; Ethylenethiourea - administration & dosage; Ethylenethiourea - toxicity; ETU; Female; fungicides; Fungicides, Industrial - metabolism; Fungicides, Industrial - toxicity; homeostasis; hypothyroidism; Hypothyroidism - blood; Hypothyroidism - chemically induced; Hypothyroidism - pathology; Hypothyroidism - physiopathology; Infertility, Female - blood; Infertility, Female - chemically induced; Infertility, Male - blood; Infertility, Male - chemically induced; iodide peroxidase; Lactation; long term effects; Low doses; Male; Medical sciences; metabolites; no observed adverse effect level; oral exposure; Pesticide Residues - toxicity; Pregnancy; Prenatal Exposure Delayed Effects; progeny; Rats; Rats, Sprague-Dawley; Reproductive toxicity; reproductive toxicology; sexual maturity; Susceptible life stages; Testosterone Congeners - blood; Thyroid; thyroid function; Thyroid Gland - drug effects; Thyroid Gland - pathology; Thyroid Gland - physiopathology; thyroid hormones; Toxicology; weaning
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.05.048

•Oral exposure to ETU is associated to effects on development, thyroid, and reproductive hormone profile in rats.•Reproductive toxicity and hypothyroidism are observed at a lower than LOAEL dose exposure in pregnant dams and F1 generation.•Pregnancy and lactation represent life stages highly susceptible to ETU exposure. Ethylenethiourea (ETU) is the common metabolite of the widely used ethylenebisdithiocarbamate fungicides. It is identified as Endocrine Disruptor given its ability to interfere with thyroid hormone biosynthesis by inhibiting thyroid peroxidase activity. As far as we know, no studies have been performed to assess potential effects of ETU exposure at low dose levels, i.e. below the established LOAEL and NOAEL, during critical phases of development. Therefore, the aim of the present study was to verify the short- and long-term effects on thyroid function, reproduction and development of oral exposure to ETU levels comparable to and lower than LOAEL/NOAEL in rats. Sixty dams were treated daily by gavage during pregnancy and lactation with 0, 0.1, 0.3, 1.0mg/kgbw per day of ETU. F1 generation was similarly treated from weaning to sexual maturity. Thyroid biomarkers were analyzed in dams and in offspring. Reproductive biomarkers were analyzed in F1 rats. For the first time this study has demonstrated reproductive toxicity and hypothyroidism at a lower than LOAEL dose exposure in pregnant dams and F1 generation. Our data suggest that even low doses of ETU can interfere with thyroid homeostasis and reproductive hormone profile if exposure starts in critical stages of development.