2. Academic Validation
  3. Assessment of the endocrine-disrupting effects of diethyl phosphate, a nonspecific metabolite of organophosphorus pesticides, by in vivo and in silico approaches

Assessment of the endocrine-disrupting effects of diethyl phosphate, a nonspecific metabolite of organophosphorus pesticides, by in vivo and in silico approaches

  • Environ Int. 2020 Feb:135:105383. doi: 10.1016/j.envint.2019.105383.
Fang-Wei Yang 1,  Guo-Ping Zhao 1,  Fa-Zheng Ren 2,  Guo-Fang Pang 3,  Yi-Xuan Li 4
Affiliations

Affiliations

  • 1 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
  • 2 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government, and Beijing Laboratory of Food Quality and Safety, China Agricultural University, Beijing 100083, China.
  • 3 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; Chinese Academy of Inspection and Quarantine, Beijing 100176, China. Electronic address: gfpang@163.com.
  • 4 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address: liyixuan9735@126.com.
PMID: 31835022 DOI: 10.1016/j.envint.2019.105383
Abstract

Organophosphorus pesticides (OPs) remain one of the most commonly used pesticides, and their detection rates and residues in agricultural products, foods and environmental samples have been underestimated. Humans and environmental organisms are at high risk of exposure to OPs. Most OPs can be degraded and metabolized into dialkyl phosphates (DAPs) in organisms and the environment, and can be present in urine as biomarkers for exposure to OPs, of which diethyl phosphate (DEP) is a high-exposure metabolite. Epidemiological and cohort studies have found that DAPs are associated with endocrine hormone disorders, especially sex hormone disorders and thyroid hormone disorders, but there has been no direct causal evidence to support these findings. Our study explored the effects of chronic exposure to DEP on endocrine Hormones and related metabolic indicators in adult male rats at actual doses that can be reached in the human body. The results showed that chronic exposure to DEP could cause thyroid-related hormone disorders in the serum of rats, causing symptoms of hyperthyroidism in rats, and could also lead to abnormal expression of thyroid hormone-related genes in the rat liver. However, DEP exposure did not seem to affect serum sex hormone levels, spermatogenesis or sperm quality in rats. The molecular interactions between DEP and thyroid hormone-related Enzymes/proteins were investigated by molecular docking and molecular dynamics methods in silico. It was found that DEP could strongly interact with thyroid hormone biosynthesis, blood transport, receptor binding and metabolism-related Enzymes/proteins, interfering with the production and signal regulation of thyroid Hormones. In vivo and in silico experiments showed that DEP might be a potential thyroid hormone-disrupting chemical, and therefore, we need to be more cautious and rigorous regarding organophosphorus chemical exposure.

Keywords

Diethyl phosphate; Endocrine-disrupting effects; Metabolite; Organophosphorus pesticides; Thyroid hormones.

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