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September 08-10, 2025 | Valencia, Spain
FAT 2019

Developmental and postnatal endocrine toxicity of tembotrione concerning plasma levels of 17 estradiol and testosterone

Davor Zeljezic, Speaker at Food Science Conferences
Institute for Medical Research and Occupational Health, Croatia (Hrvatska)
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

Biography:

Prof. Davor Zeljezic, Ph.D. obtained the Master of Science degree in the field of toxicology in 2000 at the Faculty of Science, University of Zagreb, Croatia. Doctoral thesis that he defended was in the field of genetic toxicology of pesticides. Since yet he published more than 70 scientific papers in indexed journals, with more than 1200 citations. At the moment he is the scientific advisor at the Institute for Medical Research and Occupational Health, Zagreb, Croatia. He is also the expert on behalf the Republic of Croatia in Member state committee of European Chemicals Agency (ECHA), and member of the Food enzymes scientific working group of European Food Safety Authority (EFSA). The main subject of his scientific work was pesticides’ modes of action in regards to genetic material. His research approaches were based on experiments on human cell cultures in vitro, rodent experiments in vivo and epidemiological studies comprising both, residents and occupationally exposed individuals. The methods that he applied in the work were chromosomal aberrations, micronucleus cytome assay, sister chromatid exchange assay, alkaline comet assay, hOGG1 enzyme modified comet assay, fluorescence in situ hybridization (FISH), and comet-FISH. At the moment he is the principal investigator at the project entitled Organic Pollutants in Environment - Markers and Biomarkers of Toxicity (OPENTOX), financed by Croatian Science Foundation. Besides, he leaded, collaborated as the scientist or advisor at 7 additional scientific projects. He is member of the editorial board of BioMed Research International, vicepresident of Croatian Toxicological Society, member of several national panels for projects proposal evaluation, reviewer in many scientific journals indexed in Current contents. He collaborated in the organization of domestic and international scientific conferences and held the lectures in the field of toxicology two domestic universities (Zagreb and Rijeka).

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