Endocrine disruptors in aquatic environments: evaluating the toxicity of Bisphenol-A and diethyl phthalate.

Human Exposure Estimates for Phthalates

Endocrine-disrupting chemicals (EDCs) in the aquatic environment are an emerging concern and can lead to adverse health effects on humans and aquatic life. EDCsare ubiquitous in several daily use and personal care products and ubiquitous in aquatic ecosystems. The aquatic ecosystems also serve as major sinks of EDCs and have even been found to accumulate in aquatic organisms. Fish are an important sentinel species in the aquatic system and are a reliable indication of environmental water pollution. In the present study, we have assessed the immunotoxicity effects of three important EDCs, i.e., triclosan (TCS), bisphenol A (BPA), and diethyl phthalate (DEP). There is mounting evidence that EDCs impact several physiological systems, including fish immune systems. Hence, to better understand the immune system’s complexity, we have investigated how EDCs alter the immune responses and can aggravate immunotoxicity using Labeo catla as a model fish species. The results showed significant upregulation of immune gene expression; exposure to EDCs differentially modulates immunity across the different organs (liver and brain) of Labeo catla. The present study highlighted that endocrine-disrupting compounds (TCS, BPA, and DEP) have a significant immunotoxicity effect in fish and activate several immunological pathways to control the toxic effect and maintain homeostasis. The results also indicate that immune genes can be used as a biomarker for EDC toxicity. However, further studies need to see how immune-disrupting effects happen at actual exposure levels in the environment to EDCs.

Diethyl phthalate (DEP) belongs to phthalates with short alkyl chains. It is a substance frequently used to make various products. Thus, humans are widely exposed to DEP from the surrounding environment such as food, soil, air, and water. As previously reported in many studies, DEP is an endocrine disruptor with reproductive toxicity. Monoethyl phthalate (MEP), a major metabolite of DEP in vivo, is a biomarker for DEP exposure assessment. It is also an endocrine disruptor with reproductive toxicity, similar to DEP. However, toxicokinetic studies on both MEP and DEP have not been reported in detail yet. Therefore, the objective of this study was to evaluate and develop physiologically based pharmacokinetic (PBPK) model for both DEP and MEP in rats and extend this to human risk assessment based on human exposure. This study was conducted in vivo after intravenous or oral administration of DEP into female (2mg/kg dose) and male (0.1-10mg/kg dose) rats. Biological samples consisted of urine, plasma, and 11 different tissues. These samples were analyzed using UPLC-ESI-MS/MS method. For DEP, the tissue to plasma partition coefficient was the highest in the kidney, followed by that in the liver. For MEP, the tissue to plasma partition coefficient was the highest in the liver. It was less than unity in all other tissues. Plasma, urine, and fecal samples were also obtained after IV administration of MEP (10mg/kg dose) to male rats. All results were reflected in a model developed in this study, including in vivo conversion from DEP to MEP. Predicted concentrations of DEP and MEP in rat urine, plasma, and tissue samples using the developed PBPK model fitted well with observed values. We then extrapolated the PBPK model in rats to a human PBPK model of DEP and MEP based on human physiological parameters. Reference dose of 0.63mg/kg/day (or 0.18mg/kg/day) for DEP and external doses of 0.246μg/kg/day (pregnant), 0.193μg/kg/day (fetus), 1.005-1.253μg/kg/day (adults), 0.356-0.376μg/kg/day (adolescents), and 0.595-0.603μg/kg/day (children) for DEP for human risk assessment were estimated using Korean biomonitoring values. Our study provides valuable insight into human health risk assessment regarding DEP exposure.

As the most widely used plasticizers in the world, phthalate esters (PAEs) are potential endocrine disruption compounds (EDCs). In the present study, the toxicity of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), di (2-ethylhexyl) phthalate (DEHP) on embryogenesis and larvae development of the marine univalve Haliotis diversicolor supertexta was examined in laboratory. The results show that the malformation of embryos appeared during the experiment, such as embryos died or lysed, small transparent flocculent rings studded on the periphery of the embryo, and the larvae could failed to hatch. In embryo toxic test, embryos incubated at the highest concentration of DMP, DEP and DBP solutions showed significantly high abnormal rate compared with the control, while DEHP solutions displayed no significant difference. In larval toxic test, in all concentrations of DMP, DEP and DBP solutions, larval settlement rates were low significantly than that of the control. Similarly, DEHP solutions show nearly no effect on the larval settlement. The order of toxicity on embryos and larvae is DBP>DEP>DMP>DEHP. Being a simple and easy stimulation to indoor spawn, sensitive to environmental factors, and short culture time, the embryos of H. diversicolor supertexta can be used to indicate toxicity of the PAEs.

Endocrine disruption and metabolic changes following exposure of Cyprinus carpio to diethyl phthalate

Exposure to Phthalate Esters

Background: Endocrine disruptors (EDs) are environmental chemicals that may disrupt endogenous hormones and have been linked to many adverse health outcomes including breast cancer. EDs have been shown to modulate the risk for mammary tumors in animal models, but their mechanisms at biologically relevant doses and during critical developmental windows remain poorly understood. Methods: We examined the individual and combinatorial (MIX) effects of three EDs commonly found in personal care products - diethyl phthalate (DEP), methyl paraben (MPB) and triclosan (TCS). Sprague-Dawley rats were exposed at four developmental windows - prenatal, neonatal, prepubertal and pubertal - at doses comparable to human exposure based on urinary levels reported in NHANES. Whole-transcriptome profiling was done using Affymetrix rat gene 2.0 st arrays. Results: Differential gene expression analysis by limma revealed that there were no substantial differences between the transcriptomes of prenatal and neonatal rats, so they were combined into a ‘perinatal’ group. Control rats: Expression levels of 702 transcripts significantly differed between the prepubertal and perinatal periods; gene ontology (GO) enrichment showed that GO terms related to development and response to estrogen stimuli were up-regulated and immune signaling pathways were down-regulated. Upstream analysis using Ingenuity Pathway Analysis showed that β-estradiol and estrogen receptor were among the top regulators up-regulated in the prepubertal window, and T-cell receptor and interleukins were among the top regulators down-regulated. The difference between later windows, i.e., between puberty and prepuberty was much less pronounced, with only 39 differentially expressed transcripts. ED-exposed rats: Large scale changes in mammary transcriptome were driven by developmental stage, while changes due to ED exposure appeared to be more subtle. One-way ANOVA among developmental windows demonstrated that only ∼3000 transcripts were significantly changed in DEP and MPB and ∼4000 transcripts changed in TCS and MIX compared to ∼6000 differentially expressed transcripts in control rats. Importantly, distinct signatures of genes were associated with each individual ED as well as MIX, suggesting distinctive mechanisms. Additionally, our data suggested that the pubertal window was the most susceptible; for example, 440 transcripts were differentially expressed in the MPB group relative to control only at the pubertal window and GO terms related to DNA damage and ion transport were up- and down-regulated, respectively. Conclusions: Exposure to common EDs at levels comparable to human exposure resulted in measurable changes in mammary transcriptome and reveal novel mechanisms of ED action in mammary development. Findings from our study highlight the importance of taking into account the timing of exposure when studying the relationship between environment and disease. Citation Format: Kalpana Gopalakrishnan, Qian Li, Yula Ma, Luca Lambertini, Jia Chen, Susan Teitelbaum, Fabiana Manservisi, Laura Falcioni, Luciano Bua, Fiorella Belpoggi. Effects of endocrine disruptors on rat mammary transcriptome at critical developmental windows. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5573. doi:10.1158/1538-7445.AM2015-5573

Measurement of endocrine disrupting and asthma-associated chemicals in hair products used by Black women

Comparative analysis of endocrine disrupting effects of major phthalates in employed two cell lines (MVLN and H295R) and embryonic zebrafish assay

Endocrine-disrupting chemicals used as common plastic additives: Levels, profiles, and human dietary exposure from the Indian food basket

Di (2-ethylhexyl) phthalate (DEHP), di-ethyl phthalate (DEP) and di-isononyl phthalate (DINP) are all endocrine disrupting chemicals (EDCs) for organisms. However, little research has been done on the effects of long-term EDC exposure. The present study found that the zebrafish barely grew during the 7months of DINP exposure. The fecundity rate (%) of female spawning was lower in the DEHP treatment by 4months compared to other exposure groups. Zebrafish treated with 12.5-25.0ppm of DEP for 4months presented no spawning. Gonadal-somatic index (GSI) levels significantly decreased, and there were more oocytes in the atresia and peri-nucleus stage compared to the control group. In addition, the hatching rate of embryos were 71.02%, 56.92%, and 21.70% for females treated with DINP, DEHP and DEP, respectively. There were also abnormal craniofacial chondrogenesis development on 72hpf embryos upon females treated with the three EDCs. In conclusion, long term exposure of DEHP, DINP, and DEP did not only affect the reproductive capacity of female zebrafish, but the 3 plasticizers also influence craniofacial cartilage development of its offspring.

Phthalates are known for their harmful effects on human health, including being carcinogenic, toxic, and causing endocrine disruption. Therefore, removing phthalates from aquatic environments is an important issue for researchers. This study aims to compare the efficiency of hydrogen peroxide (HP) and potassium persulfate (PS) oxidants in degrading diethyl phthalate using the oxidant-assisted subcritical water oxidation method. Additionally, the study statistically examines the effect of operational parameters (temperature, oxidant concentration, and treatment time) on diethyl phthalate degradation using the Box-Behnken design. Results indicated that temperature was the primary parameter affecting diethyl phthalate degradation, with both oxidants fitting a quadratic model. The highest total organic carbon (TOC) removal rate (100%) was achieved when potassium persulfate was used as the oxidant in the oxidation experiments. When hydrogen peroxide was used as the oxidant, the maximum TOC removal efficiency was determined to be 87%.

Impact of diethyl phthalate on freshwater planarian behaviour, regeneration, and antioxidant defence

Chronic toxicity of diethyl phthalate—A three generation lactational and gestational exposure study on male Wistar rats

Effects of bisphenol A or diethyl phthalate on cartilage development and the swimming behavior of zebrafish (Danio rerio) through maternal exposure