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.

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.

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.

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.

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.

17α-ethinylestradiol and 4-tert-octylphenol concurrently disrupt the immune response of common carp.

The aquatic environment is massively polluted with endocrine-disrupting compounds (EDCs) including synthetic estrogens (e.g. 17α-ethinylestradiol, EE2) and alkylphenols (e.g. 4-tert-octylphenol, 4t-OP). A major mechanism of action for estrogenic EDCs is their interaction with estrogen receptors and consequently their modulation of the action of enzymes involved in steroid conversion e.g. aromatase CYP19. We now studied the effects of EE2 and 4t-OP on the anti-bacterial immune response of common carp. We investigated effects on the number/composition of inflammatory leukocytes and on the gene expression of mediators that regulate inflammation and EDC binding. In vitro we found that high concentrations of both EE2 and 4t-OP down-regulated IFN-γ2 and IFN-γ-dependent immune responses in LPS-stimulated monocytes/macrophages. Similarly, during bacterial infection in fish, in vivo treated with EE2 and 4t-OP, decreased gene expression of il-12p35 and of ifn-γ2 was found in the focus of inflammation. Moreover, during A. salmonicida-induced infection in EE2-treated carp, but not in fish fed with 4t-OP-treated food, we found an enhanced inflammatory reaction manifested by high number of inflammatory peritoneal leukocytes, including phagocytes and higher expression of pro-inflammatory mediators (inos, il-1ß, cxcl8_l2). Furthermore, in the liver, EE2 down-regulated the expression of acute phase proteins: CRPs and C3. Importantly, both in vitro and in vivo, EDCs altered the expression of estrogen receptors: nuclear (erα and erß) and membrane (gpr30). EDCs also induced up-regulation of the cyp19b gene. Our findings reveal that contamination of the aquatic milieu with estrogenic EDCs, may considerably violate the subtle and particular allostatic interactions between the immune response and endogenous estrogens and this may have negative consequences for fish health.

Environmental Water Pollution, Endocrine Interference and Ecotoxicity of 4-tert-Octylphenol: A Review.

4-tert-Octylphenol is a degradation product of non-ionic surfactants alkylphenol polyethoxylates as well as raw material for a number of industrial applications. It is a multimedia compound having been detected in all environmental compartments such as indoor air and surface waters. The pollutant is biodegradable, but certain degradation products are more toxic than the parent compound. Newer removal techniques from environmental waters have been presented, but they still require development for large-scale applications. Wastewater treatment by plant enzymes such as peroxidases offers promise in total removal of 4-tert-octylphenol leaving less toxic degradation products. The pollutant's endocrine interference has been well reported but more in oestrogens than in any other signalling pathways through which it is believed to exert toxicity on human and wildlife. In this paper we carried out a review of the activities of this pollutant in environmental waters, endocrine interference and relevance to its toxicities and concluded that inadequate knowledge of its endocrine activities impedes understanding of its toxicity which may frustrate current efforts at ridding the compound from the environment.

Effects of octylphenol exposure on the lipid metabolism and microbiome of the intestinal tract of Rana chensinensis tadpole by RNAseq and 16s amplicon sequencing.

Octylphenol (OP) is a widely distributed endocrine disrupting chemical (EDC), and can be commonly found in various and diverse environmental media. Previous studies have reported that OP exposure could cause many adverse effects on aquatic animals. However, knowledge concerning the impact of OP on lipid metabolism in amphibians was still limited. In our study, Rana chensinensis tadpoles were exposed to different OP concentrations (0, 10-8, 10-7 and 10-6 mol/L) from the Gosner stage (Gs) 25-38. The RNA-seq analysis of tadpole intestines was explored by RNA-seq, and six differentially expressed genes (DEGs) related to the fat digestion and absorption were validated by RT-qPCR. Moreover, we used 16s amplicon sequencing to evaluate effects of OP on intestinal microbiome in tadpoles, further determining the variations of lipid metabolism. Our results revealed that OP exposure influenced gene expression levels related to fat digestion and absorption and led to alteration of structure and composition of intestinal microbiome. At the phylum level, the Firmicutes/Bacteroidetes ratio was gradually decreased in OP exposure groups, which disrupted lipid metabolism. According to the results of intestinal microbial functional prediction, OP exposure interfered with metabolic function and increased risk of disease. These data provide us with powerful resources to assess the effects of OP on lipid metabolism by integrating RNAseq and 16s amplicon sequencing analysis of intestinal tract and intestinal microbiome.

Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells.

There is an ample epidemiological evidence to support the role of environmental contaminants such as bisphenol A (BPA) in breast cancer development but the molecular mechanisms of their action are still not fully understood. Therefore, we sought to analyze the effects of three common contaminants (BPA; 4-tert-octylphenol, OP; hexabromocyclododecane, HBCD) on mammary epithelial cell (HME1) and MCF7 breast cancer cell line. We also supplied some data on methoxychlor, MXC; 4-nonylphenol, NP; and 2-amino-1-methyl-6-phenylimidazo [4-b] pyridine, PhIP. We focused on testing the prolonged (two months) exposure to low nano-molar concentrations (0.0015-0.0048 nM) presumed to be oncogenic and found that they induced DNA damage (evidenced by upregulation of pH2A.X, pCHK1, pCHK2, p-P53) and disrupted the cell cycle. Some agents induced epigenetic (methylation) changes of tumor suppressor genes TIMP3, CHFR, ESR1, IGSF4, CDH13, and GSTP1. Obviously, the accumulation of these molecular alterations is an essential base for cancer development. Consistent with this, we observed that these agents increased cellular invasiveness through collagen. Cellular abilities to form colonies in soft agar were increased for MCF7. Toxic agents induced phosphorylation of protein kinase such as EGFR, CREB, STAT6, c-Jun, STAT3, HSP6, HSP27, AMPKα1, FAK, p53, GSK-3α/ß, and P70S6 in HME1. Most of these proteins are involved in potential oncogenic pathways. Overall, these data clarify the molecular alterations that can be induced by some common environmental contaminants in mammary epithelial cells which could be a foundation to understand environmental carcinogenesis.

Determination and ecological risk assessment of two endocrine disruptors from River Buffalo, South Africa.

4-tert-Octylphenol (4-tOP) and triclosan (TCS) are endocrine disruptors which have been detected in environmental matrices such as air, soil and water at ultra-low levels. Exposure to endocrine disruptors may account at least in part, for the global increase in the incidence of non-communicable diseases like cancers and diabetes and may also lead to an imbalance in the aquatic ecosystem. River Buffalo is an important natural resource in the Eastern Cape of South Africa serving more than half a million people. The presence of the two compounds in the river water hitherto unknown was investigated during winter seasons using solid-phase extraction and gas chromatography-mass spectrometric techniques. The sampling points differed by some physicochemical parameters. The concentration of 4-tOP ranged 0-755 ng/L, median value 88.1 ng/L while that of TCS ranged 0-1264.2 ng/L and the median value was 82.1 ng/L. Hazard quotient as an index of exposure risk varied according to daphnids Ëƒ fish Ëƒ algae for 4-tOP exposure while HQ for TCS exposure was algae > daphnids = fish showing that both compounds were capable of causing imbalance in the aquatic ecosystem. Graphical abstract.

Octylphenol influence growth and development of Rana chensinensis tadpoles via disrupting thyroid function.

Octylphenol (OP), a class of endocrine disrupting chemicals (EDCs), could produce adverse effects on developmental process of animals. Thyroid hormone is one of the important hormones involved in animal development. To determine whether OP affect the growth and development of amphibian larvae via interfering the thyroid function, Rana chensinensis larvae at Gosner stage 29 were exposed to 10-8, 10-7 and 10-6 mol/L OP in the present study. Results demonstrated that OP could decrease the body length and mass and retard the development of tadpoles. The histologic evaluation showed microscopic structures of thyroid gland were changed in 10-7 and 10-6 mol/L OP treated groups on day 40. The expression levels of Dio2, Dio3, TRα and TRß mRNA in the liver, brain, skin and tail of tadpoles were detected by qRT-PCR, when treated with OP for 20, 30, 40 and 50 day, respectively. The results of qRT-PCR showed OP could affect the expressions of Dio2, Dio3, TRα and TRß mRNA in the four tissues, and then influence the activity and function of THs, further affecting the growth and development of the tadpoles.

A core-shell structured magnetic covalent organic framework (type Fe3O4@COF) as a sorbent for solid-phase extraction of endocrine-disrupting phenols prior to their quantitation by HPLC.

A magnetic covalent organic framework (Fe3O4@COF) with core-shell structure was fabricated at room temperature and used as an adsorbent for magnetic solid-phase extraction of polar endocrine-disrupting phenols (4-n-nonylphenol, 4-n-octylphenol, bisphenol A and bisphenol AF). The sorbent was characterized by transmission electron microscopy, FTIR, powder X-ray diffraction and other techniques. The main parameters governing the extraction efficiency were optimized. The phenols were quantified by HPLC with fluorometric detection. The method has attractive features such as low limits of detection (0.08-0.21 ng.mL-1), wide linear ranges (0.5-1000 ng.mL-1), and good repeatability (intra-day: 0.39%-4.99%; inter-day: 1.57%-5.21%). Satisfactory results were obtained when the developed method was applied to determine the four target pollutants in real world drink samples with spiked recoveries over the range of 81.3~118.0%. This indicates that the method is a powerful tool for the enrichment and determination of endocrine-disrupting phenols in drink samples. Graphical abstract A magnetite based covalent organic framework (Fe3O4@COFs) was synthesized with TPAB, TPA and Fe3O4. It was used for magnetic solid-phase extraction of endocrine-disrupting phenols from plastic-packaged tea drink samples coupled with liquid chromatography (LC) for determination.

Sorption and inhibitory effect of octylphenol ethoxylate Triton X-100 on methanogenic and denitrifying granular sludges.

The aims of this work were to characterize the sorption and evaluate the inhibitory effect of octylphenol ethoxylate Triton X-100 (OPEOTx) on methanogenic and denitrifying sludges. According to Langmuir isotherm, maximums OPEOTx sorption values on methanogenic and denitrifying sludges were 60.70 mg (gVSS)-1 and 87.47 mg (gVSS)-1 respectively. The specific removal rate of chemical oxygen demand (rCOD) and the accumulated volume biogas (VBG) were used to evaluate the OPEOTx inhibitory effect on sludges. Experimental inhibition data were fitted to the models of non-competitive inhibition and modified Gompertz. Methanogenic sludges reached higher levels inhibition in the rCOD and biogas production potential Pmax (84.0 and 88.5%) comparing with denitrifying sludges (24.3 and 21.9%). Furthermore, in all OPEOTx concentrations, carbohydrates-proteins quotient value of the extracellular polymeric substances for the denitrifying sludges remained below respect to the same quotient in methanogenic sludges. The above contributes in part to explain the greater sorption capacity of the denitrifying sludges by OPEOTx and their granules resistance to be damaged by OPEOTx amphiphilic nature. The study gives insights to understand OPEOs interactions and their effects on methanogenic and denitrifying granular sludges.

Analysis of Non-Ionic Surfactant Triton X-100 Using Hydrophilic Interaction Liquid Chromatography and Mass Spectrometry.

It is well known that surfactants increase the solubility of hydrophobic organic compounds and cause adverse environmental effects. The removal of these compounds from the contaminated soil or ground-water is particularly difficult due to their water soluble feature. In this work, an ultra-high performance hydrophilic interaction liquid chromatographic method was developed for the separation of oligomers of Triton X-100 octylphenol-polyethoxylate non-ionic surfactant. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the Triton X-100 compounds. There was a 44 mass unit difference between two adjacent peaks that is the molar mass of one ethylene oxide group (⁻CH 2 CH 2 O⁻). A quadratic retention model was applied for the estimation of retention of the examined non-ionic surfactant and the optimization of gradient elution conditions. The optimized method was suitable for the baseline separation of 28 Triton X-100 oligomers in five minutes.

Identification of in vitro effect of 4-octylphenol on the basal and human chorionic gonadotropin (hCG) stimulated secretion of androgens and superoxide radicals in mouse Leydig cells.

The aim of our in vitro study was to assess the potential effect of 4-octylphenol (4-OP) on the basal and human chorionic gonadotropin (hCG)-stimulated cholesterol levels and biosynthesis of steroid hormones in cultured mouse Leydig cells. In addition, we evaluated the intracellular superoxide production following 4-OP treatment. Isolated mouse Leydig cells were cultured in the presence or absence of 1 IU/mL (hCG) with the addition of 0.04; 0.2; 1.0; 2.5 and 5.0 µg/mL 4-OP during 44 h. The level of cholesterol was determined from the culture medium using photometry. Quantification of steroid hormones was performed by the enzyme linked immunosorbent assay and intracellular generation of superoxide radicals was assessed by the nitroblue-tetrazolium assay. Administered concentrations of 4-OP (0.04-5.0 µg/mL) did not affect basal and hCG-stimulated cholesterol level significantly. However, basal DHEA secretion was increased significantly (P < 0.001) in the highest experimental dose (5 µg/mL) of 4-OP. By hCG-stimulated DHEA secretion, a significant (P < 0.001) decrease was recorded at 5.0 µg/mL 4-OP in comparison to the control group. The stimulatory effect of 4-OP was also confirmed in androstenedione secretion, when 2.5 and 5.0 µg/mL increased hormone secretion significantly (P˂0.05; P˂0.001). Exposure to experimental concentrations (0.04 to 5.0 µg/mL) of tested chemical reduced hCG-stimulated androstenedione formation, but not significantly. Measurements of basal testosterone production have shown significant (P˂0.01; P˂0.001) increase at 1.0; 2.5 and 5.0 µg/mL of 4-OP. Furthermore, 44 h treatment by 4-OP (1.0-5.0 µg/mL) caused significant (P˂0.01; P˂0.001) intracellular accumulation of superoxide radicals in exposed cells. A considerably more detailed and systematic research is required for a better understanding of risks associated with male reproductive system in humans and wildlife.

Utilization of activated carbon for maximizing the efficiency of zirconium oxide for photodegradation of 4-octylphenol.

Utilization of AC/zirconium oxide (ZrO2) for the removal of 4-octylphenol (4-OP) from aqueous solution has been studied under simulated visible-light as a cost effective technique. To draw complete images for the prepared materials, a series of characterization methods was performed. Brunauer-Emmett-Teller (BET) data has proved that AC has high surface area and total pore volumes that are decreased after incorporation of ZrO2. Morphologically, TEM showed massive quantity of ZrO2 spherical shape nanoparticles loaded with carbon and EDX showed the uniform distribution of all the prepared materials. The photocatalytic performance has been traced via adopting a matrix effect analysis to correlate the photodegradation of 4-OP in the presence of visible light as a time function, pH, photocatalyst dose and initial concentration of 4-OP. The positive impact of AC content in AC/ZrO2 composite on the adsorption of 4-OP was strikingly observed with expanding the AC content in AC/ZrO2 composite up to 33% (wt/wt). Almost 97% of the 4-OP was removed within 180 min under simulated visible light. The optimum reaction conditions for 95% removal of 4-OP were 120 min, 1 g L-1 catalyst dose at pH 8. The photocatalytic degradation of the 4-OP was well fitted with pseudo first-order L-H kinetic model.

Evaluation of toxicity of 4-octylphenol in TM4 Sertoli cells: an in vitro study.

The reproductive toxicity of 4-octylphenol (4-OP) has been studied in animals such as mouse and fish. In humans, the exposure of sperm to 4-OP has been shown to decrease motility and viability. In this study, we performed an in vitro assessment of the toxic effects of 4-OP on mouse TM4 Sertoli cells and investigated the underlying molecular mechanisms. TM4 cells were treated with four concentrations (0, 10, 30, and 50 µM) of 4-OP at the following time points: 24, 48, and 72 h. Cell viability and apoptosis assays were conducted following 4-OP exposure. We found that 4-OP significantly decreased cell viability in a concentration- and time-dependent manner, and increased apoptosis. Quantitative PCR analysis showed that the mRNA expression levels of BCL2 Associated X, Apoptosis Regulator (Bax) and BCL2 Antagonist/Killer (Bak) increased while that of BCL2 Apoptosis Regulator (Bcl-2) decreased in 4-OP-exposed cells compared with that in the controls. Western blotting revealed that 4-OP induced caspase-3 activity and Bad phosphorylation in a concentration- and time-dependent manner. Additionally, cytochrome C protein did not colocalize with mitochondrial marker dye by 24 h. Cytochrome c protein expression increased in a time-dependent manner upon exposure to 50 µM 4-OP. These results suggest that 4-OP induces mitochondria-mediated apoptosis through regulation of Bcl-2 family proteins and caspase-3 activation in male Sertoli cells.

Molecular docking simulation on the interactions of laccase from Trametes versicolor with nonylphenol and octylphenol isomers.

The biodegradation of nonylphenol (NP) and octylphenol (OP) isomers by laccase has attracted increasing concerns. However, the interaction mechanism between these isomers and laccase remains unclear, especially for fungal laccase. In this work, molecular docking was employed to study this issue. The results indicated that the structural characteristic of alkyl chain (position and branching degree) affected the interactions between Trametes versicolor (T. versicolor) laccase and isomers. The binding affinity between them was closely related to the position and branching degree of alkyl chain in isomers. The binding affinities between linear isomers and T. versicolor laccase were para-position < meta-position < ortho-position. For selected branched 4-NP, the isomers with bulky α-substituent in alkyl chain had higher binding affinities. In addition, hydrophobic contacts between T. versicolor laccase and NP or OP isomers were necessary, while H-bonds were optional. The isomers with similar structure may have more common residues involved in hydrophobic contacts. The H-bonds of selected NPs and OPs were all connected with phenolic hydroxyl. These findings provide an insight into detailed interaction mechanism between T. versicolor laccase and isomers of NP and OP. It is helpful to broaden the knowledge of degradation technology of NPs and OPs and provide theoretical basis on biological remediation of these contaminants.

Job-exposure matrix for the assessment of alkylphenolic compounds.

OBJECTIVES: Our aim was to develop a job-exposure matrix (JEM) to assess occupational exposure to alkylphenolic compounds in epidemiological research, considering changes in their use over time, and including exposure probabilities in the assessments. METHODS: We consulted multiple sources of information, and performed interviews with 9 key people from industry and academia. 3 hygienists coded frequency (minority or majority of workers involved) and intensity of exposure (including dispersive processes, with shaking, or aerosol generation, or otherwise) to alkylphenolic compounds for all the 390 International Standard Classification of Occupations (ISCO)-88 job titles by period of time. Intensity and frequency of exposure were combined in a single score as follows: unlikely=0, occasionally+low intensity=1, occasionally+high intensity=2, frequent+low intensity=2, and frequent+high intensity=3. RESULTS: We identified 54 (13.8%) of the 390 ISCO-88 job titles with potential exposure to alkylphenolic compounds. In 6 of jobs deemed as exposed, exposure depended on the economic sector of the occupation. Nonylphenol ethoxylates were the compounds most commonly involved (30 job titles, 55.6% of the exposed). Variations in alkylphenolic compounds use varied greatly over time; while they are still used in the plastic and rubber industry, in domestic cleaning agents their use began to decline before 1995. CONCLUSIONS: We built a JEM to assess exposure to alkylphenolic compounds, taking into account changes in use over time, different types of alkylphenolic compounds and different scenarios of exposure, which can be a valuable tool for exposure assessment in epidemiological research on the health effects of these chemicals.

Glucuronidation of 4-tert-octylphenol in humans, monkeys, rats, and mice: an in vitro analysis using liver and intestine microsomes.

4-tert-Octylphenol (4-tOP) is an endocrine-disrupting chemical. It is mainly metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the glucuronidation of 4-tOP in humans, monkeys, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of 4-tOP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and monkeys, and the biphasic model for rats and mice. The K m, V max, and CL int values of human liver microsomes were 0.343 µM, 11.6 nmol/min/mg protein, and 33.8 mL/min/mg protein, respectively. The kinetics of intestine microsomes followed the Michaelis-Menten model for humans, monkeys, and rats, and the biphasic model for mice. The K m, V max, and CL int values of human intestine microsomes were 0.743 µM, 0.571 nmol/min/mg protein, and 0.770 mL/min/mg protein, respectively. The CL int values estimated by Eadie-Hofstee plots were in the order of mice (high-affinity phase) (3.0) > humans (1.0) ≥ monkeys (0.9) > rats (high-affinity phase) (0.4) for liver microsomes, and monkeys (10) > mice (high-affinity phase) (5.6) > rats (1.4) > humans (1.0) for intestine microsomes. The percentages of the CL int values of intestine microsomes to liver microsomes were in the order of monkeys (27 %) > rats (high-affinity phase in liver microsomes) (7.9 %) > mice (high-affinity phase in liver and intestine microsomes) (4.2 %) > humans (2.3 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward 4-tOP markedly differ among species and imply that species differences are strongly associated with the toxicities of alkylphenols.