Title : Developmental and postnatal endocrine toxicity of tembotrione concerning plasma levels of 17 estradiol and testosterone
Abstract:
Tembotrione is herbicide belonging to a family of aromatic ketones. It is a relatively newly developed substance used for post-emergent control of broad-leaved and grassy weed. It acts by depleting of carotenoids which deprives chlorophyllit and has been designed to overcome cornfield toxicity of earlier herbicides of this class. Though its formulation has been based on leptospermone, a naturally occurring substance produced by plants themselves, it exhibits adverse effects in non-target organisms. Being relatively short time on the market, assessments of possible effects of long-term exposure at low doses of tembotrione have not been assessed yet. Thus, we conducted the study to evaluate possible adverse effects on most sensitive members in every population: offsprings. More particularly, we measured level of sex hormones (17β-estradiol and testosterone) in Wistar rat pups of both sexes of dams treated with tembotrione. To observe transplacental effects treatment started with first day of gastation and newborns were sacrificed on day of the birth. To observe both transplavental and translactational effect on sex hormones the treatment was prolonged till since first day of gestation until weaning when pups’ blood samples were collected. To evaluated the solemn translactational effect of tembotrione dams were treated from birth until weaning. Also, prepuberty blood samples were taken and levels of sex hormones were measured. In all experiments dams were treated in consecutive days by gavage with three doses relevant to realistic human exposure and derived from toxicological referent values for ADI (0.0004 mg/kg b.w./day), NOAEL (0.0007 mg/kg b.w./day), and 1/500 LD50 (4.0 mg/kg b.w./day). The hormone levels were measured in plasma by the enzyme-linked immunosorbent assay (ELISA) using Estradiol rat ELISA and Testosterone rat/mouse ELISA Kit DEMEDITEC Diagnostics GmbH (Kiel, Germany). The absorbance was read at 450 nm. In mail newborns and pups, transplacental and translactational exposure to tembotrion, respectively, significantly increased serum levels of testosterone (2.0±0.2 vs 0.4±0.1 and 2.0±0.4 vs 1.6±0.5 ng/ml, respectively). Prolonged exposure during both, gestation and lactation did not affect the testosterone levels (2.6±0.5 ng/ml), while in prepuberty pups testosterone was significantly lower (2.2±0.6 ng/ml) than in negative controls (4.6±0.9 ng/ml). In newborn female rats levels of 17β-estradiol were higher at lower doses (72.3±4.2 vs 56.5±3.5 pg/ml) but significantly decreased at 1/500 LD50 (3.4±0.7 vs 2.6±0.3 pg/ml). In plasma of weaned and prepuberty female pups levels of estrogen were not affected (3.0±0.7 vs 4.9±1.3 and 1.4±0.2 vs 1.6±0.4 pg/ml, respectively). Following 48 consecutive days treatment with any of tembotrion doses levels of testosterone (0.2±0.0 vs 0.5±0.2 ng/ml) and estrogen (18.3±1.7 vs 16.4±2.2 pg/ml) in dams remained unaffected. Based on the results we may conclude that transplancental and translactational exposure of offsprings to different doses of tembotrione may affect plasma levels of 17β-estradiol and testosterone. Discrepancies in the effects between lower and highest dose of tembotrion indicate important role of metabolic activity of placenta and dams’ livers. They indicate that higher doses may lead to metabolic overload of placenta and its abort. Nevertheless, observed effects may pose significant risk for proper development of primary sexual properties, sexual dysfunction and infertility
