Association of alkylphenols exposure with serum liver function markers in pregnant women in Guangxi, China.

The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (<13 weeks, mean gestation=9.80±1.96 weeks) and late (≥32 weeks, mean gestation = 37.23±2.45 weeks) pregnancies from 219 pregnant women in the Guangxi Zhuang birth cohort from 2015-2017. We also examined the serum levels of APs in these pregnant women in early pregnancy. The present study aimed to investigate the correlations between the exposure of pregnant women to APs and their serum liver function indices. The results of the generalized linear model (GLM) in this study revealed that nonylphenol (NP) was positively correlated with total bilirubin (TBIL) (P=0.04) in early pregnancy, and 4-n-nonylphenol (4-N-NP) was negatively correlated with glutamyl transferase (GGT) (P=0.012). In late pregnancy, NP was positively associated with TBIL (P=0.002), and 4-tert-octylphenol (4-T-OP) was positively correlated with alanine aminotransferase (ALT) (P=0.02). Restricted cubic spline (RCS) results revealed doseresponse relationships between NP and TBIL (Poverall=0.011) and between 4-N-NP and GGT (Poverall=0.007) in early pregnancy. In late pregnancy, there were doseresponse relationships between NP and TBIL (Poverall=0.001) and between 4-T-OP and ALT (Poverall=0.033). There was also a doseresponse relationship between NP volume and GGT with an inverted 'U' shape (Poverall=0.041, Pnonlinear=0.012). Bayesian kernel machine regression modeling (BKMR) revealed that TBIL increased significantly (P<0.05) with increasing levels of coexposure to APs in both early and late pregnancy. Overall, exposure to APs during pregnancy affects maternal liver function to varying degrees. The present study provides new epidemiological evidence that exposure to alkylphenols in pregnant women interferes with liver function.

Selective biodegradation of octylphenol polyethoxylates with different ethoxylate length chains by aerobic bacterial culture.

Octylphenol polyethoxylates (OPEOn) are composed of a hydrophobic octylphenol (OP) group and a hydrophilic polyethylene oxide (EO) chain and are widely used in commercial products. Shorter EO chains and OPEOn biometabolites have been identified as endocrine-disrupting contaminants and can threaten biotic factors in the ecosystem. In this study, OPEOn at three EO lengths (TX-45, TX-114, and TX-165) were selected in monomer (MN) or micelle (MC) state for batch experiments under aerobic conditions, with results showing biodegradation rates of 90 % within 35-70 h. The pseudo-first-order constant (k) of OPEOn biodegradation was observed in the order TX-45 (0.1414 h-1) > TX-114 (0.0556 h-1) > TX-165 (0.0485 h-1), with biomineralisation reaching at least 80 % for all OPEOn. The selective biodegradation of EO chains was also measured, with initial accumulation of OPEO3 observed along with the depletion of longer EO chains for TX-45 and TX-114 in both the MN and MC states. A similar trend was observed for the MN state of TX-165, with OPEO3-OPEO9 observed to accumulate and reduced after 70 h. MC biodegradation was accomplished via the initial accumulation of OPEO3-OPEO9. The amounts of OPEO3 increased and others reduced; however, OPEO3 remained high at the end of biodegradation for TX-165. Bacterial community analysis indicated that the genera Sphingobium spp., Pseudomonas spp., Flavobacterium spp., Comamonas spp., and Sphingopyxis spp. dominate OPEOn biodegradation, and they have their roles during biodegradation, and the community-level physiological profile (CLPP) was also changed by biodegradation in both the MN and MC states.

Effects of crosstalk between steroid hormones mediated thyroid hormone in zebrafish exposed to 4-tert-octylphenol: Estrogenic and anti-androgenic effects.

Alkylphenols, such as nonylphenol and 4-tert-octylphenol (OP), are byproducts of the biodegradation of alkylphenol ethoxylates and present substantial ecological and health risks in aquatic environments and higher life forms. In this context, our study aimed to explore the effect of OP on reproductive endocrine function in both female and male zebrafish. Over a period of 21 days, the zebrafish were subjected to varying concentrations of OP (0, 0.02, 0.1, and 0.5 µg/L), based on the lowest effective concentration (EC10 = 0.48 µg/L) identified for zebrafish embryos. OP exposure led to a pronounced increase in hepatic vitellogenin (vtg) mRNA expression and 17ß-estradiol biosynthesis in both sexes. Conversely, OP exhibits anti-androgenic properties, significantly diminishes gonadal androgen receptor (ar) mRNA expression, and reduces endogenous androgen (testosterone and 11-ketotestosterone) levels in male zebrafish. Notably, cortisol and thyroid hormone (TH) levels demonstrated concentration-dependent elevations in zebrafish, influencing the regulation of gonadal steroid hormones (GSHs). These findings suggest that prolonged OP exposure may result in sustained reproductive dysfunction in adult zebrafish, which is largely attributable to the intricate reciprocal relationship between hormone levels and the associated gene expression. Our comprehensive biological response analysis of adult zebrafish offers vital insights into the reproductive toxicological effects of OP, thereby enriching future ecological studies on aquatic systems.

Lycium barbarum polysaccharides attenuate nonylphenol and octylphenol-induced oxidative stress and neurotransmitter disorders in PC-12 cells.

Nonylphenol (NP) and octylphenol (OP) are environmental contaminants with potential endocrine disrupting effects. However, there is limited research on the mechanisms and intervention of combined NP and OP exposure-induced neurotoxicity. This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250 µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8 µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information regulation type 1 (SIRT1), monoamine oxidase A (MAOA), phosphorylated cyclic-AMP response binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase receptor type B (p-TrkB). However, N-acetyl-L-cysteine (NAC) treatment counteracted the changes of signalling molecule p38, SIRT1/MAOA and CREB/BDNF/TrkB pathways-related proteins induced by NP and OP. LBP pretreatment ameliorated combined NP and OP exposure-induced oxidative stress and neurotransmitter imbalances. Furthermore, the application of LBP and administration of a p38 inhibitor both reversed the alterations in the signaling molecule p38, as well as the proteins associated to the SIRT1/MAOA and CREB/BDNF/TrkB pathways. These results implied that LBP may have neuroprotective effects via p38-mediated SIRT1/MAOA and CREB/BDNF/TrkB pathways.

Sex differences in 4-tert-octylphenol toxicokinetics: Exploration of sex as an effective covariate through an in vivo modeling approach.

4-tert-octylphenol (4-tert-OP) is a potentially harmful substance, which is found widely in the environment. Nevertheless, information on the in vivo toxicokinetics of 4-tert-OP is lacking, and quantitative risk assessment studies are urgently needed. Therefore, we aimed to quantitatively identify differences in the toxicokinetics of 4-tert-OP and its distribution among tissues between sexes. To this end, following exposure of male and female rats to 10 or 50 mg/kg 4-tert-OP orally and 4 or 8 mg/kg 4-tert-OP intravenously, we conducted a quantitative analysis of samples using ultra-high performance liquid chromatography-tandem mass spectrometry. The results revealed that the 4-tert-OP plasma concentration profiles differed between sexes; however, systemic absorption of 4-tert-OP through the gastrointestinal tract occurred within 0.5 h of exposure in both sexes. Although small, the excretion percentage of 4-tert-OP in urine and feces was lower in males than females (0.06-0.08% vs. 0.82-1.11% of exposure). Significant sex differences were also confirmed in the tissue distribution patterns of 4-tert-OP, and overall, the average tissue distribution in males was lower than that in females. The distribution of 4-tert-OP to liver, adipose, spleen, kidney, brain, and lung in both sexes was predominant. A covariate exploration modeling approach revealed that sex explained the differences in 4-tert-OP toxicokinetics between sexes. These significant differences in the toxicokinetics and tissue distribution of 4-tert-OP between sexes will be important for the scientific precision human risk assessment of 4-tert-OP.

Head dysgenesis and disruption of cranial neural crest stem cells behaviour by 4-octylphenol in fire-bellied toad Bombina orientalis embryos.

Alkylphenolic endocrine disruptors (Eds) have been known to affect development of the descendants of multipotent neural crest cells (NCCs) in amphibian embryos. To unravel the mechanism of head dysgenesis induced by alkylphenols in amphibians, the effect of 4-octylphenol (OP) on the differentiation of cranial NCCs in developing embryos and tadpoles, ex vivo NC explant, and isolated NCCs was examined in fire-bellied toad Bombina orientalis with 0, 1, 2, 5, 10, 25 and 50 µM concentrations. Following OP treatment, head cartilages were frequently absent together with the decreased col2a1 mRNA level in tadpoles. While the lipid hydroperoxide (LPO), endoplasmic reticulum stress (ERS), apoptosis, and DNA fragmentation were significantly increased in stage 22 neulurae and heads of stage 45 tadpoles. In stage 22 neulurae, OP decreased sox9 mRNA, the master transcription factor for chondrogenic differentiation and increased undifferentiated NCC markers. The ectopic NCCs were found in endoderm while mesodermal SOX10(+) cells were decreased. In cranial NCCs isolated from stage 22 embryos, OP treatment decreased cellular survival and increased apoptosis, epithelial-mesenchymal transition (EMT) and cell migration. In chondrogenic induced cranial NC explants, OP treatment decreased SOX9(+) chondrocytes and cartilage development. Together, OP potentiated oxidative damage, apoptosis, EMT, and ectopic migration of NCCs. Considering that tissue differentiation requires stem cells to activate the molecular mechanism of differentiation at the correct location during embryonic development, these changes caused by OP may inhibit sox9-dependent chondrogenic differentiation of cranial NCCs, leading to head dysgenesis in B. orientalis embryos. Therefore, developing multipotent NCCs could be an important target of OP, provides new direction for the estimation of the risk of EDs exposure in human and wildlife animals.

Long-Chain Alkylphenol Biodegradation Potential of Soil Ascomycota.

A total of 11 ascomycete strains destructing technical nonylphenol (NP) and 4-tert-octylphenol (4-t-OP) were isolated from NP-contaminated soddy-podzolic loamy soil (Leningrad Region, Russia). The isolates proved capable of degrading NP and 4-t-OP at a high load (300 mg/L). The most efficient Fusarium solani strain 8F degraded alkylphenols (APs) both in cometabolic conditions and in the absence of additional carbon and energy sources. A decrease in APs was due to biodegradation or biotransformation by the strain and, to a minor extent, absorption by fungal cells. NP and 4-t-OP half-lives were, respectively, 3.5 and 6.4 h in cometabolic conditions and 9 and 19.7 h in the absence of additional carbon and energy sources. Amounts of the lipid peroxidation product malondialdehyde (MDA) and reduced glutathione (GSH) increased during NP and 4-t-OP biodegradation in cometabolic conditions by 1.7 and 2 times, respectively, as compared with a control. A high GSH level in F. solani 8F cells potentially implicated the metabolite in both AP biodegradation and strain resistance to oxidative stress. The study is the first to report on the NP and 4-t-OP degradation by the ascomycete F. solani in cometabolic conditions and in the absence of additional carbon and energy sources. The high AP degradation potential of soil ascomycetes was assumed to provide a basis for new environmentally safe bioremediation technologies for purification of soils and natural and waste waters contaminated with endocrine disruptors.

The Association between 4-Tertiary-Octylphenol, Apoptotic Microparticles, and Carotid Intima-Media Thickness in a Young Taiwanese Population.

As one of the most common alkylphenols, 4-tertiary-octylphenol (4-tOP) is commonly used in many consumer products. Our previous epidemiological study revealed a negative correlation between serum 4-tOP levels and carotid intima-media thickness (CIMT), which serves as a biomarker of arteriosclerosis. We aimed to explore the role of apoptotic microparticles, markers of vascular endothelial cell function, in the 4-tOP and CIMT connection. To investigate this, we enrolled 886 Taiwanese adolescents and young adults (aged 12-30 years) and examined the relationships among serum 4-tOP levels, apoptotic microparticles (CD31+/CD42a-, CD31+/CD42a+), and CIMT. Our results showed negative associations among serum 4-tOP levels, both apoptotic microparticles, and CIMT in multiple linear regression analysis. The odds ratios for CIMT (≥75th percentile) and the natural logarithm of 4-tOP were highest when both CD31+/CD42a- and CD31+/CD42a+ were greater than the 50th percentile. Conversely, the odds ratios were lowest when both CD31+/CD42a- and CD31+/CD42a+ were less than the 50th percentile. In the structural equation model, we demonstrated that serum 4-tOP levels were negatively correlated with CIMT and indirectly and negatively correlated with CIMT through both apoptotic microparticles. In conclusion, our study reported the inverse association between 4-tOP apoptotic microparticles and CIMT in a young Taiwanese population. Further experimental studies are needed to clarify these associations.

A meta-analysis of the occurrence of alkylphenols and alkylphenol ethoxylates in surface waters and sediments in the United States between 2010 and 2020.

Nonylphenol (NP), Octylphenol (OP), and their ethoxylates (NPEO and OPEO) have been the subject of considerable scientific and regulatory attention, primarily due to concerns about their aquatic toxicity and endocrine activity. Environmental monitoring has been conducted and reported for these substances in the United States (U.S.) for several decades. This paper develops an updated statistically based meta-analysis of the occurrence and ecological relevance of these substances in fresh and marine surface waters and sediments in the U.S. between 2010 and 2020. The overall objectives of this study were: (1) to evaluate the impact of analytical detection limits (DLs) and treatment of censored or non-detected (ND) samples on reported results, (2) to summarize and evaluate recent (2010-2020) occurrence and concentrations of these substances in surface waters and sediments, (3) to conduct an ecological screening assessment of the potential risks of these substances to aquatic organisms in surface waters and sediments for this same period, and (4) to examine temporal trends of these substances in surface waters and sediments relative to previous investigations. Given that a large proportion of all NP, NPEO, OP and OPEO samples in recent (2010-2019) U.S. monitoring studies were below their respective method Limit of Detection/Limit of Quantification (LOD/LOQ) detection frequency ranging from 0 to 24%), proxy values were imputed using robust regression of order statistics (ROS). Nationally, NP and OP concentrations in fresh surface waters and sediments have decreased from 2010 to 2019. In contrast, changes in NP and OP concentrations in marine waters and sediments were more variable with some increases noted. A screening environmental risk assessment indicated that less than 1% of all samples exceeded U.S. or Canadian environmental quality guidelines. No exceedances were noted after 2016 which indicates a low potential for risk to aquatic organisms.

Alkylphenols cause cytotoxicity and genotoxicity induced by oxidative stress in RTG-2 cell line.

Alkylphenols ethoxylates are industrial surfactants, and the release in the environmental matrices produces degraded products, of which nonylphenol (NP) and octylphenol (OP) were the most common. They can be classified as endocrine disruptors since the estrogenic potential is widely recognized, but some others toxic aspects are in discussion. This study aimed to evaluate the toxicity of NP, OP, and mixtures of both through cellular, biochemical and genetic biomarkers in fish gonadal cell line RTG-2 exposed to nominal concentrations of 0.05; 0.5; 5; 50, and 100 µg mL-1 of each chemical and their mixtures of 0.05, 0.5; 5 µg mL-1 concentrations. After 24 h, the cells were collected for cytotoxic (neutral red - NR; crystal violet - CV, resazurin assay - RA and lactate-dehydrogenase - LDH), antioxidant system (glutathione-s-transferase - GST; superoxide-dismutase - SOD; glutathione-peroxidase - GPx and malondialdehyde - MDA) and genotoxic assays (alkaline comet assay and Fpg-modified alkaline comet assay). The chemicals and their mixtures were cytotoxic at 50 and 100 µg mL-1, in general aspect, but LDH showed cytotoxicity since 0.05 µg mL-1. The GST and SOD showed an activity increase trend in most tested groups, while GPx decreased at 5 µg mL-1 of the mixture. The MDA increase in all groups resulted in lipid peroxidation. The reactive oxygen species caused DNA damage for all groups. The tested chemicals and concentrations have been found in the freshwater systems. They can induce cell toxicity in several parameters that could impair the gonadal tissues considering the RTG-2 responses.

Development of an HPLC-DAD method for the simultaneous analysis of four xenoestrogens in water and its application for monitoring photocatalytic degradation.

A high-performance liquid chromatography with diode array detector (HPLC-DAD) method was developed and validated for the simultaneous quantification of 4 xenoestrogens in water for monitoring their photocatalytic degradation in synthetic water. The analytical parameters evaluated were linearity, limits of detection, and quantification (LODs and LOQs), selectivity, and accuracy, according to the US Food and Drug Administration (FDA) and Eurachem guidelines. The developed method shows good linearity (R2 > 0.995 for all compounds), and LODs ranged from 0.02 to 0.04 mg L-1, while LOQs ranged from 0.05 to 0.11 mg L-1. Moreover, accuracy expressed as recovery and precision were within the required limits. Therefore, the developed method was considered accurate, and reliable. In addition, it was successfully applied for monitoring a mixture of 4 xenoestrogens in water during the photocatalytic treatment.•An HPLC-DAD method was developed to quantify 4 xenoestrogens in water simultaneously.•The developed HPLC-DAD method shows excellent linearity, selectivity, and accuracy.•A mixture of 4 xenoestrogens was reliably monitored during their photocatalytic degradation.

Amphibian Metamorphosis Assay: Investigation of the potential effects of five chemicals on the hypothalamic-pituitary thyroid axis of Xenopus laevis.

2-Ethylhexyl 4-hydroxybenzoate (2-EHHB), 4-tert-octylphenol (4-OP), 4-nonylphenol-branched (4-NP), benzyl butyl phthalate (BBP) and dibutyl phthalate (DBP) were evaluated using a 21-day Amphibian Metamorphosis Assay (AMA). Xenopus laevis larvae were exposed nominally to each chemical at 3.6, 10.9, 33.0, and 100 µg/L, except 4-NP concentrations were 1.8, 5.5, 16.5 and 50 µg/L. Endpoints included mortality, developmental stage, hind limb length (HLL), snout-vent length (SVL), body weight (BW), and thyroid histopathology. BBP and 4-OP accelerated development compared to controls at the mean measured concentration of 3.5 and 39.8 µg/L, respectively. An increase in developmental stage frequency distribution was observed for 4-OP at 39.8 and 103 µg/L, BBP at all concentrations and DBP at 143 µg/L. Normalized HLL was increased on study day (SD) 21 for all tested substances except 4-NP. Histopathology revealed accelerated development and mild thyroid follicular cell hypertrophy at all BBP concentrations, but moderate severity at 105 µg/L. Increased BW occurred for all chemicals except 4-OP. Increased SVL was observed for 4-NP, BBP and DBP on SD 21. There was insufficient evidence that 4-NP and 2-EHHB affected the hypothalamic-pituitary thyroid axis, however, BBP, DBP and 4-OP showed potential effects on amphibian metamorphosis and thyroid activity, albeit through different lines of evidence.

Simultaneous Quantification of Bisphenol-A and 4-Tert-Octylphenol in the Live Aquaculture Feed Artemia franciscana and in Its Culture Medium Using HPLC-DAD.

Aquaculture, a mass supplier of seafood, relies on plastic materials that may contain the endocrine disruptors bisphenol-A (BPA) and tert-octylphenol (t-OCT). These pollutants present toxicity to Artemia, the live aquaculture feed, and are transferred through it to the larval stages of the cultured organisms. The purpose of this work is the development and validation of an analytical method to determine BPA and t-OCT in Artemia and their culture medium, using n-octylphenol as the internal standard. Extraction of the samples was performed with H2O/TFA (0.08%)-methanol (3:1), followed by SPE. Analysis was performed in a Nucleosil column with mobile phases A (95:5, v/v, 0.1% TFA in H2O:CH3CN) and B (5:95, v/v, 0.08% TFA in H2O:CH3CN). Calibration curves were constructed in the range of concentrations expected following a 24 h administration of BPA (10 µg/mL) or t-OCT (0.5 µg/mL), below their respective LC50. At the end of exposure to the pollutants, their total levels appeared reduced by about 32% for BPA and 35% for t-OCT, and this reduction could not be accounted for by photodegradation (9-19%). The developed method was validated in terms of linearity, accuracy, and precision, demonstrating the uptake of BPA and t-OCT in Artemia.

Relationship between exposure of alkylphenols in serum of pregnant women during early pregnancy and adverse birth outcomes.

Alkylphenols are a type of endocrine disruptors, which are commonly found in personal care products, food, and water and are more harmful to the human body. To investigate the relationship between exposure of alkylphenols in serum of pregnant women during early pregnancy and adverse birth outcomes, a total of 2035 healthy pregnant women and their neonates were recruited in the birth cohort of Zhuang nationality in Guangxi from 2015 to 2018. The peripheral venous blood samples were collected from pregnant women in early pregnancy; the concentrations of nonylphenol (NP), 4-nonylphenol (4-N-NP), 4-tert-octylphenol (4-T-OP), and 4-n-octylphenol (4-N-OP) in serum were detected by ultra-performance liquid performance chromatography-tandem mass spectrometry (UPLC-MS). Binary logistic regression showed that NP [OR = 1.40 (95% CI: 1.00, 1.94)] was positively associated with preterm birth. Restricted cubic spline analyses showed that logNP and log4-T-OP had non-linearity associations with preterm birth (logNP: Poverall = 0.006, Pnon-linear = 0.003; log4-T-OP: Poverall = 0.004, Pnon-linear = 0.002). Multiple linear regression analysis showed that maternal serum concentration of NP was negatively associated with birth weight of perinatal infants (ß = -14.68, 95% CI: -29.18, -0.19), which may be sensitive in male neonates (ß = -26.18, 95% CI: -47.33, -5.02). The findings demonstrate that nonylphenol is a risk factor of preterm birth, and nonylphenol is negatively associated with the birth weight in male infants.

Biomonitoring of bisphenol A, 4-nonylphenol, and 4-t-octylphenol in Turkish population: exposure and risk assessment.

Biomonitoring studies are important tools to understand the effects of endocrine-disrupting compounds on human health. Up to now, there have been no biomonitoring and risk assessment studies conducted in Turkish population in which urinary bisphenol A (BPA), 4-nonylphenol (4-NP), and 4-t-octylphenol (4-t-OP) levels were measured simultaneously. The aim of this study is to measure urinary BPA, 4-NP, and 4-t-OP on Turkish population and conduct a risk assessment using urinary levels of chemicals of interest. During the study, liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to measure urinary levels of above-mentioned chemicals, and human biomonitoring was used as a risk assessment tool in 103 volunteers, living in Mersin Region, Turkey. Urinary BPA, 4-NP, and 4-t-OP were founded as 0.0079 µg/g creatinine, 0.0177 µg/g creatinine, and 0.0114 µg/g creatinine, respectively. The obtained estimated daily intakes (EDIs) were calculated as 0.095 µg/kg bw/day, 0.041 µg/kg bw/day, and 0.091 µg/kg bw/day, for BPA, 4-NP, and 4-t-OP, respectively. In conclusion, although no potential health risk due to BPA and 4-NP exposure was observed, there might be health risks associated with 4-t-OP exposure in the Turkish population.

Simple monitoring of endocrine-disrupting chemicals using transgenic Arabidopsis plants expressing medaka estrogen receptor.

Endocrine-disrupting chemicals (EDCs) are widespread contaminants that severely affect the endocrine systems of living organisms. In addition to the conventional instrument-based approaches for quantifying organic pollutants, a monitoring method using transgenic plants has also been proposed. Plants carrying a recombinant receptor gene combined with a reporter gene represent a system for the easy detection of ligands that specifically bind to the receptor molecule. Here, the EDC detection sensitivity of transgenic Arabidopsis plants expressing the medaka (Oryzias latipes) estrogen receptor (mER) and green fluorescent protein (GFP) genes, was assessed. Four transgenic Arabidopsis lines, obtained by transformation with expression plasmids constructed using combinations of two types of the ligand-binding domains of mER, the DNA-binding domain of LexA and the transactivation domain of VP16 in the chimeric receptors, showed significant induction of GFP when germinated on a medium contaminated with 1 ng/mL 4-t-octylphenol (OP). The most sensitive XmEV19-2 plants detected 0.1 ng/mL OP and 1 pg/mL 17ß-estradiol. GFP expression was suppressed by the insecticides imidacloprid and fipronil, whereas perfluorooctanesulfonic acid induced it at 0.1 ng/mL. Experiments with river water-based medium showed that XmEV19-2 can be used for monitoring polluted waters, detecting OP at concentrations as low as 5 ng/mL. Notably, XmEV19-2 showed a significant decrease in root length when grown on 0.1 ng/mL OP. mER transgenic plants can be a promising tool for simple monitoring of EDCs, without the need for extraction and concentration steps in sample preparation.

Single and mixture toxicity evaluation of three phenolic compounds to the terrestrial ecosystem.

Endocrine-disrupting chemicals (EDCs) are primarily studied regarding endocrine-mediated effects in mammals and fish. However, EDCs can cause toxicity by mechanisms outside the endocrine system, and, as they are released continuously into soils, they may pose risks to terrestrial organisms. In this work, the plant Allium cepa and the earthworm Eisenia foetida were used as test systems to evaluate the toxicity and cyto-/geno-toxicity of three environmental phenols known as EDCs (Bisphenol A - BPA, Octylphenol - OP, Nonylphenol - NP). The tested phenols were evaluated in environmentally relevant concentrations (µg/L) and in single forms and mixture. BPA, OP, and NP did not inhibit the seed germination and root development in A. cepa in their single forms and mixture. However, all single forms of the tested phenols caused cellular and DNA damages in A. cepa, and although these effects persist in the mixtures, the effects were verified at lower levels. These phenols caused acute toxicity to E. foetida after 48 h of exposure and at both conditions evaluated (single forms and mixture); however, unlike A. cepa, in earthworms, mixtures and single forms presented the same level of effects, indicating that interspecies physiological different might influence the mixture toxicity. In summary, our results suggest that BPA, OP, and NP are toxicants to earthworm and cyto-/geno-toxicants to monocotyledonous plants at low concentrations. However, interaction among these phenols reduces the magnitude of their individual effects (antagonistic effect) in the plant test system. Therefore, this study draws attention to the need to raise knowledge about the ecotoxicity of phenolic compounds to help predict their ecological risks and protect non-target terrestrial species.

Influence of octylphenol on gene expression of gonadotropins and their receptors, testicular structure and mating behavior of male Rana chensinensis.

In the present study, responses of the Chinese brown frog (Rana chensinensis) to exposure to different doses and duration of Octyphenol (OP) which degraded from alkylphenol ethoxylates (APEs) were characterized during the adult periods. The effects of OP on growth, development and reproduction and the expression of genes in gonad were investigated. The expression levels of fshß, lhß, fshr and lhr had significant differences as the exposure time increased. The pathological and morphological changes were also observed in the OP treatments. Furthermore, the number of TUNEL positive cells and the TUNEL index was elevated after exposed to OP. Besides that, OP treatment could influence its mating behavior and reduce the fertilization rates. Taken together, these results indicated that OP disrupt sex steroid signaling, normal development of spermatogenesis, courtship behavior of male frogs and decline fertilization rate in R. chensinensis.

Alkyphenol Exposure Alters Steroidogenesis in Male Lizard Podarcis siculus.

BACKGROUND: Nonylphenol (NP) and Octylphenol (OP) are persistent and non-biodegradable environmental contaminants classified as endocrine disruptor chemicals (EDCs). These compounds are widely used in several industrial applications and present estrogen-like properties, which have extensively been studied in aquatic organisms. The present study aimed to verify the interference of these compounds alone, and in mixture, on the reproductive cycle of the male terrestrial vertebrate Podarcis siculus, focusing mainly on the steroidogenesis process. METHODS: Male lizards have been treated with different injections of both NP and OP alone and in mixture, and evaluation has been carried out using a histological approach. RESULTS: Results obtained showed that both substances are able to alter both testis histology and localization of key steroidogenic enzymes, such as 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß- hydroxysteroid dehydrogenase (17ß-HSD) and P450 aromatase. Moreover, OP exerts a preponderant effect, and the P450 aromatase represents the major target of both chemicals. CONCLUSIONS: In conclusion, NP and OP inhibit steroidogenesis, which in turn may reduce the reproductive capacity of the specimens.

Binding mechanism of 4-octylphenol with human serum albumin: Spectroscopic investigations, molecular docking and dynamics simulation.

4-Octylphenol (OP) is an environmental estrogen that can enter organisms through the food chain and cause various toxic effects. Here, the interaction between OP and human serum albumin (HSA) was explored through multipectral, molecular docking and dynamics simulation. The results showed that OP and HSA formed a ground state complex through a static quenching mechanism, and the interaction was spontaneously driven by hydrogen bonds and hydrophobic interaction forces. The binding constant at different temperatures was measured to be on the order of 105 L mol-1. Site competition experiments suggested that OP interacted with amino acid residues Lys195, Cy245 and Cys246 located at the Sudlow site I of HSA, resulting in a more stretched protein peptide. The presence of OP increased the surface hydrophobicity of HSA, and reduced the content of α-helix in HSA by 3.4%. FT-IR spectra showed that OP interacted with the C=O and C-H groups of the polypeptide backbone. Molecular docking demonstrated that OP mainly bound to Site I of HSA and hydrogen bonds participated in the interaction. In addition, molecular dynamics simulations further explored the stability and dynamic behavior of the OP-HSA complex through RMSD, RMSF, SASA and Rg.