Effects Of Alkylphenols Research Articles

Effects of alkylphenols on the biotransformation of diuron and enzymes involved in the synthesis and clearance of sex steroids in juvenile male tilapia (Oreochromus mossambica)

Previous studies using in vivo bioassay guided fractionation indicated that the herbicide diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) and alkylphenol (AP)-containing surfactants were detected in fractions of extracts that induced the estrogenic biomarker, vitellogenin in fish exposed to surface water extracts from the United States. However, when the compounds were evaluated individually using in vivo estrogenic assays or in vitro estrogen receptor assays, estrogenic activity was not observed. Since APs have been shown to alter activity and content of cytochrome P450s (CYP) which convert diuron to potential estrogenic metabolites, the hepatic biotransformation of diuron was measured with and without a 7day pretreatment of p-Octylphenol (OP) and p-Nonylphenol (NP) at low (OP 13ng/L+NP 91ng/L), and high concentrations (OP 65ng/L+NP 455ng/L) in juvenile male Nile tilapia (Oreochromus niloticus). Pre-treatment with the OP/NP (AP) mixture caused elevated levels of NADPH-catalyzed formation of 3,4-dichlorophenyl-N-methylurea (DCPMU) but not 3,4-dichlorophenylurea (DCPU). Fish were also treated with nominal concentrations of low (40ng/L) and high (200ng/L) diuron and each of its three degradates/metabolites: DCPMU, DCPU and 3,4-dichloroaniline (DCA). Additional treatments were conducted with APs and Diuron as a mixture at the low concentrations which mimicked concentrations observed in surface waters. Hepatic vitellogenin (Vtg) mRNA was induced by exposure to the high concentrations of Diuron, as well as DCPMU and DCPU in both concentrations. Brain cytochrome P450 aromatase activity was generally diminished by diuron, its metabolites, and the AP/diuron mixtures. 17β-Hydroxysteroid dehydrogenase (17βHSD) levels were also reduced by DCPMU and DCA in the lower concentrations, but not by higher concentrations. While the AP mixture reduced 17βHSD, the AP/diuron mixture induced testosterone (T) biosynthesis at the single concentration tested. Although CYP3A expression was induced by all diuron metabolites, it was unchanged by the AP mixture. These data indicate that mixtures of AP and diuron enhanced the formation of the metabolite (DCPMU) which induced vitellogenin, and reduced T biosynthetic enzymes (17βHSD inhibition). Overall, these data showed that APs may have induced the biotransformation of diuron to at least one metabolite, that may disrupt androgen biosynthesis and potentially alter steroid feedback pathways in the central nervous system.

Asphaltene aggregation and impact of alkylphenols.

The main objective of this study was to provide novel insights into the mechanism of asphaltene aggregation in toluene/heptane (Heptol) solutions and the effect of alkylphenols on asphaltene dispersion through the integration of advanced experimental and modeling methods. High-resolution transmission electron microscope (HRTEM) images revealed that the onset of asphaltene flocculation occurs near a toluene/heptane volume ratio of 70:30 and that flocculates are well below 1 μm in size. To assess the impact of alkylphenols on asphaltene aggregation, octylphenol (OP) and dodecylphenol (DP) were evaluated by impedance analysis based on their ability to delay the precipitation onset and to reduce the size of nonflocculated asphaltene aggregates in 80:20 toluene/heptane solutions. Although a longer dispersant chain length did not affect the precipitation onset, it reduced the size of the aggregates. Molecular dynamics simulations were then performed to understand the mechanism of interaction between a model asphaltene and OP in heptane. OP molecules saturated the H-bonding sites of asphaltenes and prevented them from interacting laterally between themselves. This explained why OP favored the formation of flocculates with filamentary rather than globular structures, which were clearly observed by HRTEM. Although OP proved to be an effective dispersant, its effectiveness was hindered by its self-association and the fact that it interacted at the periphery of asphaltenes, leaving their aromatic cores uncovered.

127 TREATMENTS WITH DIVERSE ENDOCRINE-DISRUPTING CHEMICALS RESULTED IN THE INHIBITION OF OVARIAN TUMOR PROGRESSION VIA INTERRUPTION OF TRANSFORMING GROWTH FACTOR-β IN IN VITRO AND XENOGRAFTED MOUSE MODELS

Activated oestrogen receptor (ER) signaling pathway by 17β-estadiol (E2) appeared to suppress transforming growth factor β (TGF-β) signaling pathway by cross-talk with TGF-β components in ER-positive cancer cells. In this study, we further examined the inhibitory effects of alkylphenols, including 4-nonylphenol (NP), 4-otylphenol (OP), bisphenol A (BPA), and benzophenon-1 (BP-1), in TGF-β signaling pathway. The transcriptional and translational levels of TGF-β-related genes were examined by reverse-transcription PCR (RT-PCR), Western blotting analysis in xenografted mouse models of ovarian cancer BG-1 cells. The NP, OP, and BPA induced the expression of snoN, a TGF-β pathway inhibitor. Treatment with NP, BPA, and BP-1 resulted in decreased phosphorylation of Smad3, a downstream target of TGF-β. With these 2 effects, NP and BPA stimulated the proliferation of BG-1 cells via inhibition of the TGF-β signaling pathway. In a xenograft mouse model, transplanted BG-1 ovarian cancer cells showed significantly decreased phosphorylation of Smad3 and increased expression of snoN in the ovarian tumour masses following treatment with E2, NP, or BPA. In parallel with an in vitro model, the expressions of TGF-β signaling pathway were similarly regulated by NP or BPA in a xenograft mouse model, revealing consistent results. Taken together, these results support that NP and BPA may cause the disruption of the TGF-β signaling pathway and increase the risk of oestrogen-dependent cancers such as ovarian cancer. This work was supported by a grant from the Next-Generation BioGreen 21 Program (No. PJ009599), Rural Development Administration, Republic of Korea.

The Effect of Alkylphenols on Lobster Shell Hardening

Alkylphenols, anthropogenic estrogenic endocrine disruptors in vertebrates, have been found in lobsters (Homarus americanus) in New England sites. We hypothesize that alkylphenols interfere in the shell hardening during molting. We used an in vitro cuticle bioassay to investigate the effects of 2 alkylphenolic compounds—2,4-bis-(dimethylbenzyl) phenol (compound 3) and bisphenol A (BPA; 4,4#-dihydroxy-2,2-diphenylpropane (also referred to as 4,4#-(propan-2-ylidene) diphenol))—on tyrosine incorporation during the hardening of new cuticle following lobster molting. During sclerotization, both alkylphenols and cold tyrosine competed with C 14 -tyrosine incorporation in a concentration-dependent manner. This process was also phenoloxidase dependent, as treatment with phenylthiourea (PTU; a phenoloxidase inhibitor) significantly decreased C 14 -tyrosine incorporation. We also found that incorporation of C 14 -2,4-bis-(dimethylbenzyl) phenol during the shell hardening process was inhibited by cold alkylphenol, cold tyrosine, or PTU, and competition was concentration dependent. Furthermore, incorporation of tyrosine and derivatives into new cuticle decreased with time after molting from 27% incorporation 1 day after a molt to 6% by 4 days after a molt. In nonmolting cuticles, there was no incorporation of alkylphenol or tyrosine derivatives. When lobsters were injected with 2,4-bis-(dimethylbenzyl) phenol during the premolt stage, it took the shells 12 ± 1 days to harden sufficiently to resist deflection by 5 lb pressure exerted by a pressure gauge, compared with 7 ± 1 days for control shells. Thus, shell hardening is delayed significantly by the presence of 2,4-bis-(dimethylbenzyl) phenol. The effects of this compound on shell hardening may result in lobsters susceptibility to microbial invasion and, therefore, may contribute to the onset of shell disease.

Effect of alkylphenols from Phagnalon rupestre on trinitrochlorobenzene-induced hypersensitivity

Effect of alkylphenols from Phagnalon rupestre on trinitrochlorobenzene-induced hypersensitivity

Effects of alkylphenols on glycerophospholipids and cholesterol in liver and brain from female Atlantic cod ( Gadus morhua)

Offshore oil production releases large amounts of lipophilic compounds in produced water into the ocean. In 2004, 143 million m 3 produced water, containing approximately 13 tons of long-chain (> C 4) alkylphenols (AP), was discharged from installations in the Norwegian sector of the North Sea. Long-chain APs are known to cause endocrine disruption in a number of species. However, relatively little is known about their long-term effects in the marine environment. In the present study, Atlantic cod ( Gadus morhua) were exposed (0.02 to 80 mg AP/kg) to a mixture (1:1:1:1) of APs (4- tert-butylphenol, 4- n-pentylphenol, 4- n-hexylphenol and 4- n-heptylphenol) or 17 β-estradiol (5 mg E2/kg) for 5 weeks and the effect on the fatty acid profile and cholesterol content in the membrane lipids from the liver and the brain was studied. We also determined the interaction between different para-substituted APs and glycerophospholipids (native phospholipids extracted from cod liver and brain) and model phosphatidylcholine (PC 16:0/22:6 n-3) in monolayers with the Langmuir–Blodget technique. The study demonstrated that APs and E2 alter the fatty acid profile in the polar lipids (PL) from the liver to contain more saturated fatty acids (SFA) and less n-3 polyunsaturated fatty acids (n-3 PUFA) compared with control. In the brain of the exposed groups a similar effect was demonstrated, although with higher saturation of the fatty acids found in the neutral lipids (mainly cholesterol ester), but not in the polar lipids. The AP and E2 exposure also gave a decline in the cholesterol levels in the brain. The in vitro studies showed that APs increased the mean molecular areas of the PLs in the monolayers at concentrations down to 5 μM, most likely due to intercalation of the APs between PL molecules. The increase in molecular area increased with the length of the alkyl side chain.

Is there a linkage between bioaccumulation and the effects of alkylphenols on male breams (Abramis brama)?

There was some evidence from a previous study that estrogenic disruptors, like alkylphenols, could effect fish in the small River Saar of Southwestern Germany. Concentrations of 4NP and 4NP1EO found in breams (Abramis brama) in the Saar River were much higher than those found in other sampling sites of the German Environmental Specimen Bank, including those from sampling sites in the Rivers Elbe, Rhine, Mulde, and Saale and in Lake Belau. We studied the relationship between accumulation and effect using vitellogenin (vtg) and a hepatosomatic index (HSI) of estrogenic effects and by measuring concentrations of AP and APE accumulated in breams caught at six sampling sites in the River Saar and one in the River Mosel. To link these results with those of the previous study we standardized our sampling efforts to obtain comparable data. Elevated vtg levels were found in the breams at all sampling sites near to or downstream of sewage plant discharges, whereas low vtg levels corresponded to sampling sites not influenced by municipal waste water. While HSI values did not correspond to the location of sampling sites, there was a weak but statistically significant correlation to vtg concentrations. Concentrations of four AP and APE were much more lower, as in the previous study, and were neither linked with sewage treatment plant discharges nor correlated with vtg levels. In conclusion, a linkage between accumulation and the effects of AP and APE could not be established, but the relationship between elevated vtg concentrations and municipal waste water, which contains other important endocrine disruptors, was clear.

Effects of alkylphenols on redox status in first spawning Atlantic cod ( Gadus morhua)

Offshore oil production releases large amounts of lipophilic compounds in produced water and into the ocean. The discharge of produced water from the Norwegian petroleum sector has increased from 26 million m 3 in 1993 to 120 million m 3 in 2001, and it continues to increase. Produced water contains significant amounts of alkylphenols, which have been reported to be estrogenic, causing endocrine disruption in fish. In year 2000, approximately 44 tons of alkylphenols were released on the Norwegian continental shelf in connection with discharge of produced water. Except from being estrogenic, relatively little is known about the effects of alkylphenols when released in the marine environment. Our objective was to study how alkylphenols affect the redox status in first spawning Atlantic cod ( Gadus morhua) of both sexes. Model compounds tested included 4- tert-butylphenol (C 4), 4-n-pentylphenol (C 5), 4-n-hexylphenol (C 6) and 4-n-heptylphenol (C 7), all found in produced water. First spawning Atlantic cod were force-fed a mixture of these four alkylphenols, ranging between 0.02 and 80 ppm or 5 ppm 17β-estradiol (E 2), for 1 or 4 weeks. Increased hepatic total glutathione concentration in response to alkylphenol exposure was detected in female fish compared to control group after 1-week exposure, an effect not seen after 4 weeks. Furthermore, hepatic total glutathione concentration was sex dependent, where male fish sampled after 4 weeks had higher levels of glutathione than female fish. Increased glutathione reductase catalytic activities in both male and female fish were seen after exposure to 0.02 ppm alkylphenol mixture in 4 weeks. The glutathione S-transferase activity was only affected in male fish exposed to 0.02 ppm alkylphenols, and glucose-6-phosphate dehydrogenase activity increased in female fish exposed to 0.02 ppm alkylphenol mixture for 1 week. The increase of hepatic total glutathione content as well as the effects on glutathione reductase activities suggests that alkylphenol exposure affects the redox status in Atlantic cod.

Effects of alkylphenols on redox status in first spawning Atlantic cod (Gadus morhua)

Offshore oil production releases large amounts of lipophilic compounds in produced water and into the ocean. The discharge of produced water from the Norwegian petroleum sector has increased from 26 million m3 in 1993 to 120 million m3 in 2001, and it continues to increase. Produced water contains significant amounts of alkylphenols, which have been reported to be estrogenic, causing endocrine disruption in fish. In year 2000, approximately 44 tons of alkylphenols were released on the Norwegian continental shelf in connection with discharge of produced water. Except from being estrogenic, relatively little is known about the effects of alkylphenols when released in the marine environment. Our objective was to study how alkylphenols affect the redox status in first spawning Atlantic cod (Gadus morhua) of both sexes. Model compounds tested included 4-tert-butylphenol (C4), 4-n-pentylphenol (C5), 4-n-hexylphenol (C6) and 4-n-heptylphenol (C7), all found in produced water. First spawning Atlantic cod were force-fed a mixture of these four alkylphenols, ranging between 0.02 and 80 ppm or 5 ppm 17β-estradiol (E2), for 1 or 4 weeks. Increased hepatic total glutathione concentration in response to alkylphenol exposure was detected in female fish compared to control group after 1-week exposure, an effect not seen after 4 weeks. Furthermore, hepatic total glutathione concentration was sex dependent, where male fish sampled after 4 weeks had higher levels of glutathione than female fish. Increased glutathione reductase catalytic activities in both male and female fish were seen after exposure to 0.02 ppm alkylphenol mixture in 4 weeks. The glutathione S-transferase activity was only affected in male fish exposed to 0.02 ppm alkylphenols, and glucose-6-phosphate dehydrogenase activity increased in female fish exposed to 0.02 ppm alkylphenol mixture for 1 week. The increase of hepatic total glutathione content as well as the effects on glutathione reductase activities suggests that alkylphenol exposure affects the redox status in Atlantic cod.

Effects of alkylphenols on CYP1A and CYP3A expression in first spawning Atlantic cod ( Gadus morhua)

Alkylphenols are continuously released into the ocean as a result of offshore oil production. Alkylphenols, including 4- tert-butylphenol (C 4), 4 n-pentylphenol (C 5), 4 n-hexylphenol (C 6), and 4 n-heptylphenol (C 7), up to 237 ppb concentrations, have been detected in produced water from oil platforms. Previous studies have shown that alkylphenols induce vitellogenesis in fish. Atlantic cod ( Gadus morhua) of both sexes were force-fed with various doses ranging between 0.02 and 80 ppm of a mixture of alkylphenols (C 4:C 5:C 6:C 7 ratio 1:1:1:1) or 5 ppm 17β-estradiol. We investigated effects on hepatic CYP1A and CYP3A protein expression in protein blots, using antibodies against scup ( Stenotomus chrysops) CYP1A1 and rainbow trout ( Oncorhynchus mykiss) CYP3A. There was a sexually dimorphic expression of CYP1A and CYP3A protein levels, with females expressing higher levels than males. Treatment of male Atlantic cod with 17β-estradiol resulted in increased CYP1A and CYP3A protein levels. Exposure to alkylphenols resulted in a dose-dependent increase of CYP1A and CYP3A protein expression in males, but not in females. However, this increase of CYP1A protein levels was not reflected on the CYP1A-mediated ethoxyresorufin- O-deethylase (EROD) activity, implying that alkylphenols inhibited the CYP1A enzyme activity in vivo. In vitro inhibition studies with pooled liver microsomes from Atlantic cod confirmed that the alkylphenols mixture efficiently inhibited the CYP1A activity (IC 50=10 μM), although the inhibitory effect of each individual alkylphenol varied. The IC 50 values for each individual alkylphenol on the CYP1A activity were, in a descending order of magnitude: [C 7>C 6>C 5⪢C 4], ranging from 12 to 300 μM with decreased length of the 4-alkyl chain. The effect of alkylphenols on the CYP3A activity in vitro in liver microsomes also was investigated, using the fluorescent 7-benzyloxy-4-[trifluoromethyl]-coumarin (BFC) as a diagnostic CYP3A substrate. The alkylphenol mixture inhibited CYP3A activity with IC 50 value at 100 μM. The IC 50 values for each individual alkylphenol on CYP3A activity were, in a descending order of magnitude: [C 5>C 6>C 7>C 4], ranging between 60 and 250 μM. Taken together, our results show that the alkylphenol mixture and 17β-estradiol resulted in elevated hepatic CYP1A and CYP3A expression in male Atlantic cod. The alkylphenol mixture strongly inhibited CYP1A activities, whereas it weakly inhibited CYP3A activity in Atlantic cod liver microsomes in vitro. In addition, 17β-estradiol was a weak inhibitor of CYP3A activity (IC 50=75 μM) and did not notably inhibit the CYP1A activity in vitro.

Effect of alkylphenols on adult male medaka: plasma vitellogenin goes up to the level of estrous female

The effect that oral administration of four alkylphenols, (1) bisphenol A (BPA), (2) p-t-octylphenol (OP), (3) p-nonylphenol (NP) and (4) p-n-nonylphenol ( n-NP), as well as 17α-ethynylestradiol (EE2) had on male medaka fish vitellogenin was investigated. The male medaka was fed diets containing different concentrations of these chemicals for 7 days, after which their plasma vitellogenin levels were measured. Vitellogenin levels up to ≈10 7 ng/ml were found. This value is close to that of the normal estrous female medaka. The median effective concentration (EC 50) values resulting from BPA, OP, NP and EE2 in the diet were calculated as 1600, 2600, 940 and 0.37 μg/g diet, respectively.

Effects of 4- tert-octylphenol, 4- tert-butylphenol, and diethylstilbestrol on prenatal testosterone surge in the rat

In the present study, we evaluated the effects that 4- tert-octylphenol (OP) and 4- tert-butylphenol (BP) had on the prenatal testicular testosterone surge at embryonic day (ED) 19.5 in the rat. In utero exposure to alkylphenols (0.1–100 mg/kg maternal weight) on EDs 13.5, 15.5, and 17.5 did not decrease testicular testosterone content, whereas exposure to diethylstilbestrol (DES) caused a significant depression in testosterone synthesis and secretion. The depression was maintained during ex vivo tissue culture. In order to elucidate the observed differences in the in vivo effects between alkylphenols and DES, the exposures were also carried out in tissue culture of intact ED 19.5 testes. Basal testosterone, progesterone, cAMP production and hCG-induced testosterone levels were determined during and after a 3-h culture period. DES (100 mg/l) did not alter testosterone production but caused a two-fold increase in progesterone. OP (10, 100, 500 mg/l) and BP (100 mg/l) significantly increased testosterone and progesterone levels by up to seven-fold. In the presence of BP 100 mg/l, however, the intratesticular testosterone content did not correlate with the significantly increased fraction of secreted, or leaked, testosterone. The latter was correlated with tissue damage observed at electron microscopic level. Consistent with this, BP 500 mg/l elevated testicular testosterone level slightly during the first hour in the culture but the level subsequently returned to the control value. At the electron microscopic level, alkylphenols caused most severe changes in Leydig cell membrane structures and lipid droplets. In the DES-treated testes, membrane vesicle formation around the lipid droplets and increased mitochondrial pleiomorphy were observed. Altogether, the present in vivo and in vitro analyses confirm different effects of alkylphenols and DES on fetal rat steroidogenesis and tissue structure.

Effect of alkylphenols on colloidal structure of detergent-dispersant additives

The work reported here is a continuation of a previous study* of the intermolecular interaction of alkylphenols present in salicylate and phenolic additives with the active substance of the additive. The starting materials in this work were neutral calcium additives of three types: the salicylate additive Detersol 50 (calcium alkylsalicylate, designated AS-Ca), the sulfonate additive Lubrizol 52 (calcium alkylbenzenesulfonate, designated ABS-Ca), and the alkylphenolsulfonate additive (APS-Ca). From these additives, the active substance (indicated in parentheses) was recovered by chromatograpy on silica gel. We also investigated the overbased additives Detersol 140 (As-Ca+CaCO~) and Lubrizol 74 (ABS-Ca-CaCO3), from which the active substance was recovered by precipitation with acetone.

Effect of alkylphenols on operating characteristics of alkylsalicylate additives

Effect of alkylphenols on operating characteristics of alkylsalicylate additives

Effect of Alkyl Phenols on the Storage and Manifold Stability of Gasolines

The effects of a number of different alkyl phenols on various gasoline properties were investigated. One of the properties investigated was storage stability. Gasoline-additive blends were aged in amber glass bottles at either 60/sup 0/C or 70/sup 0/C in an atmosphere of oxygen, or at 43/sup 0/C (110/sup 0/F) in an atmosphre of air. Deterioration of the gasoline was estimated from the increase in air jet gum and from changes in other properties. Few data on the results of the storage tests are included.