4-Nonylphenol

Other Classes -> Phenols

Waste-water effluent contaminant

log Kow = 5.76

5.76

In water, 7 mg/L at 25 °C

Insoluble in water

Soluble in benzene, carbon tetrachloride, heptane

0.007 mg/mL at 25 °C

317 °C

Pale-yellow, viscous liquid; slight phenolic odor. Specific gravity: 0.950 at 20 °C/20 °C. BP: 293 °C. FP: -10 °C (sets to glass below this temperature). Viscosity: 563 cP at 20 °C... Insoluble in water; soluble in most organic solvents /Nonylphenol, 25154-52-3/

This chemical does not meet GHS hazard criteria for 67.6% (447 of 661) of all reports.

Danger

H302 (32.2%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P264, P264+P265, P270, P273, P280, P301+P317, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P318, P321, P330, P363, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 661 reports by companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

Chemical: Phenol, 4-nonyl-

Hazard Traits - Endocrine Toxicity

SP - indicates a substance that is identified in a proposed Significant New Use Rule.

Status: Active Update: 07-03-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/17497

Substance: p-nonylphenol

Phenol, 4-nonyl-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date: 3/29/96; Reporting date: 5/29/96.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 4-Nonylphenol is included on this list. Effective date: 3/29/96; Sunset date: 6/30/98.

Acute Tox. 4 (32.2%)

Acute toxicity - category 4

Hazardous to the aquatic environment (Acute) - Category 1

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

4-Nonylphenol was detected in 51% of 371 urine samples collected in the US with a median concentration of <0.1 ug/L(1). 4-Nonylphenol was detected in adipose, liver and brain tissue of eleven autopsy patients in 2002 in Antwerp, Belgium at <0.004-0.161, <0.003-1.401 and <0.004-0.009 ng/g wet weight, respectively(2). In hair samples collected from 42 people residing in Pomerania, Poland, 4-nonylphenol was detected at 5.4-23,829.5 ng/g dry weight(3). 4-Nonylphenol was detected in three Japanese human milk samples at 0.65-1.4 ng/g(4).

Lysophosphatidic acid (LPA) signaling via G protein-coupled transmembrane LPA receptors (LPA1 to LPA6) mediates a variety of cellular functions, including cell proliferation, migration, morphogenesis, and differentiation. Recently, we demonstrated that the different induction of LPA receptors by estrogens regulates cell motile activity of rat liver epithelial WB-F344 cells. In the present study, to assess whether endocrine disruptors (EDs) are involved in cellular functions through LPA signaling, we measured cell motile activity and LPA receptor expressions in WB-F344 cells treated with bisphenol A (BPA) and 4-nonylphenol (4-NP). Using quantitative real time RT-PCR analysis, the Lpar1 expression was elevated in BPA-treated cells, whereas the Lpar3 expression was decreased. In contrast, 4-NP increased the Lpar3 expression, but not the Lpar1 and Lpar2. For cell motility assay with a Cell Culture Insert, cell motile activity of BPA-treated cells was significantly lower than that of untreated cells. In contrast, 4-NP markedly enhanced cell motile activity. The effects of BPA and 4-NP on cell motility were inhibited by the Lpar1 or Lpar3 knockdown. These results suggest that BPA and 4-NP may regulate cell motile activity through the different induction of LPA receptors in WB-F344 cells.

Contaminant exposure in aqueous systems typically involves complex chemical mixtures. Given the large number of compounds present in the environment, it is critical to identify hazardous chemical interactions rapidly. The present study utilized a prototype for a novel high-throughput assay to quantify behavioral changes over time to identify chemical interactions that affect toxicity. The independent and combined effects of 2 chemicals, diazinon (an insecticide) and 4-nonylphenol (a detergent metabolite), on the swimming behavior of the freshwater crustacean Daphnia pulex were examined. Cumulative distance and change in direction were measured repeatedly via optical tracking over 90 min. Exposure to low concentrations of diazinon (0.125-2 uM) or 4-nonylphenol (0.25-4 uM) elicited significant concentration- and time-dependent effects on swimming behavior. Exposure to 0.5 uM 4-nonylphenol alone did not significantly alter mean cumulative distance but did elicit a small, significant increase in mean angle, the measure of change in direction. When 0.5 uM 4-nonylphenol was used in combination with diazinon (0.125-0.5 uM), it augmented the adverse impact of diazinon on the swimming behavior of Daphnia. Additionally, enhanced sensitivity to diazinon was observed in animals exposed to treated wastewater effluent for 24 hr prior to a diazinon challenge. The present experiments demonstrate that exposure to 4-nonylphenol and complex chemical mixtures (e.g., treated wastewater) can enhance the toxicity of exposure to the insecticide diazinon.

EC50; Species: Scenedesmus subspicatus (Green Algae); Conditions: freshwater, static; Concentration: 870 ug/L for 72 hr; Effect: decreased population growth />98% purity/

EC50; Species: Scenedesmus subspicatus (Green Algae); Conditions: freshwater, static; Concentration: 424000 ug/L for 49-72 min; Effect: population decreased photosynthesis /formulation/

EC50; Species: Pseudokirchneriella subcapitata (Green Algae) exponential growth phase strain 22662, axenic culture; Conditions: freshwater, static, 23 °C, pH 7.35-8.3, hardenss 32-641 mg/L CaCO3; Concentration: 500 ug/L for 72 hr; Effect: population decreased biomass /85% purity/

EC50; Species: Pseudokirchneriella subcapitata (Green Algae) exponential growth phase strain 22662, axenic culture; Conditions: freshwater, static, 23 °C, pH 8.2, hardenss 48.4 mg/L CaCO3; Concentration: 530 ug/L for 72 hr; Effect: population decreased biomass /85% purity/

For more Ecotoxicity Values (Complete) data for 4-Nonylphenol (46 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 6900-53,300(2-4) indicate that 4-nonylphenol is expected to be immobile in soil(SRC). Volatilization of 4-nonylphenol from moist soil surfaces is expected(SRC) given an estimated Henry's Law constant of 3.4X10-5 atm-cu m/mole(SRC), based upon its vapor pressure, 8.18X10-4 mm Hg(5), and water solubility, 7 mg/L(6). However, adsorption to soil is expected to attenuate volatilization(SRC). 4-Nonylphenol is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(5). 4-Nonylphenol is expected to biodegrade rapidly in soil based on degradation of >90% in 20 days(6); however, the field dissipation half-life of 4-nonylphenol in soils treated with centrifuge dried biosolids and lagoon dried biosolids was 257 and 248 days, respectively(7).

AQUATIC FATE: Based on a classification scheme(1), Koc values of 6900-53,300(2-4) indicate that 4-nonylphenol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(5) based upon an estimated Henry's Law constant of 3.4X10-5 atm-cu m/mole(SRC), derived from its vapor pressure, 8.18X10-4 mm Hg(6), and water solubility, 7 mg/L(7). Using this Henry's Law constant and an estimation method(5), volatilization half-lives for a model river and model lake are 1.8 and 17 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 1.3-9.6 years if adsorption is considered(8). According to a classification scheme(9), BCFs of 15-1300 measured in a variety of fish(10-12), suggest bioconcentration in aquatic organisms is low to very high depending on the species. Based on the biodegradation of 4-nonylphenol in seawater of about 50% after 58 days, 4-nonylphenol is expected to biodegrade in the aqueous environment(13).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4-nonylphenol, which has a vapor pressure of 8.18X10-4 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 4-nonylphenol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 7.5 hours(SRC), calculated from its rate constant of 5.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). 4-Nonylphenol does not absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Reproductive Toxin - A chemical that is toxic to the reproductive system, including defects in the progeny and injury to male or female reproductive function. Reproductive toxicity includes developmental effects. See Guidelines for Reproductive Toxicity Risk Assessment.

IDENTIFICATION AND USE: 4-Nonylphenol (4-NP) is a pale yellow viscous liquid. It is routinely used as a co-stabilizer with mixed-metal stabilizers for heat stabilization during plastic production. It is also used as starting material for the production of phenolic resins. HUMAN STUDIES: 4-NP is a ubiquitous environmental toxin that is formed as a byproduct in the manufacturing and/or sewage treatment of regular household items. Due to its hydrophobic nature, 4-NP can easily accumulate in living organisms, including humans, where it displays a wide range of toxic effects. 4-NP appears to increases the risk of developing inflammatory bowel disease by promoting or prolonging adverse progression of inflammation in the gastrointestinal tract. Prolonged exposure to 4-NP through the diet may lead to local damage at the level of intestinal mucosa, with potentially negative consequences for intestinal homeostasis and functionality. Exposure to 4-NP may contribute to autoimmune susceptibility and/or exacerbate existing autoimmune conditions by affecting normal expression of cytokines. ANIMAL STUDIES: Nonylphenol produced severe injury when tested externally on the eyes of rabbits. In mice 4-NP perturbed key regulators of adipogenesis and lipogenic pathway in vivo. Perinatal exposure to 4-NP increased body weight, fat mass, and serum total cholesterol and glucose levels in offspring. 4-NP may be expected to increase the incidence of obesity and can act as a potential chemical stressor for obesity and obesity-related disorders. In rats perinatal exposure to 4-NP affects the adipogenesis in both male and female F1 offspring, and this effect can be progressed to the F2 offspring through the maternal line. The genotoxicity of 4-NP was evaluated by using the D7 strain of Saccharomyces cerevisiae. The results showed that 4-NP induced significant cytotoxic effect on S. cerevisiae cells at 50 mg/L, as well as mutagenic effects at the lowest tested concentrations (12 and 25 mg/L). ECOTOXICITY STUDIES: On the basis of in vitro and in vivo animal studies 4-NP is considered an endocrine disrupting chemical (EDC). For example, build-up of 4-NP in exposed mussels and an overall decrease of 17-beta-estradiol and testosterone levels were demonstrated. In sole (Solea solea) both plasma vitellogenin level and estrogen receptor beta (ERbeta) mRNA expression were increased in tested animals following a short exposure to environmental relevant concentrations (10(-6) M) of 4-NP. In zebrafish, 4-NP is able to disrupt the notochord morphogenesis, muscle function and the neuroendocrine system during embryonic development. The analysis of plasma sex steroid levels revealed a significant increase in 17beta-estradiol and testosterone in plasma of 4-NP exposed juvenile males and females of rainbow trout, respectively. Furthermore, a significant increase was observed in plasma cortisol levels. On the other hand, 4-NP decreased both plasma triiodothyronine and thyroxine after 7 and 14 days of treatment. In Bombyx mori larvae constantly fed 4-NP at concentrations ranging from 0.05 to 0.4 g/kg gonad development was retarded and maturity was decreased in both male and female pupae, while the sex ratio was unaffected by 4-NP exposure.

/BIRDS and MAMMALS/ The uptake and effects of contaminants were measured in the insectivorous tree swallow (Tachycineta bicolor) at a wastewater treatment site. The study examined reproductive, immunological, and growth endpoints in tree swallows exposed to chlorinated hydrocarbon contaminants and to 4-nonylphenol in wastewater lagoons at the Iona Wastewater Treatment Plant, Vancouver (BC, Canada). Clutch size was significantly lower in tree swallows breeding at Iona Island in 2000 and 2001 compared to the reference site. In 2000, fledging success was significantly lower and mean mass of nestling livers was significantly higher in the tree swallows breeding at the Iona Island Wastewater Treatment Plant. Additional factors that may influence reproductive success, such as parental provisioning and diet composition, did not differ significantly between sites. Levels of 4-nonylphenol detected in sediment and insects were elevated at the Iona Island Wastewater Treatment Plant (2000: lagoon sediment 82,000 ng/g dry weight, insects 310 ng/g wet weight; 2001: lagoon sediment 383,900 ng/g dry weight, insects 156 ng/g wet weight) compared to the reference site (2000: pond sediment 1,100 ng/g dry weight, insects not sampled; 2001: pond sediment 642 ng/g dry weight, insects 98 ng/g wet weight). These results indicate that tree swallows might be a useful indicator species for exposure to 4-nonylphenol at wastewater treatment sites; however, further work is necessary to determine the extent of uptake and effects of 4-nonylphenol in riparian insectivorous birds.

/AQUATIC SPECIES/ The present study investigated in vivo and in vitro effects of environmental relevant concentrations of 4-nonylphenol (100-750 ng/L) on the reproduction of rainbow trout (Oncorhynchus mykiss). To determine the effect of 4-nonylphenol on semen quality rainbow trout were exposed to three concentrations of 4-nonylphenol in a flow-through system during the spawning period (60 days). At an estimated 4-nonylphenol concentration of 750 ng/L semen production was completely inhibited, at 280 and 130 ng/L the semen production was significantly reduced in comparison to the control. Sperm density, sperm motility and sperm fertility were not affected. Also the development of embryos and larvae at the end of yolk sac stage was affected by 4-nonylphenol. At estimated 4-nonylphenol exposure levels of 280 and 750 ng/L the percentage of eyed stage embryos was slightly but significantly lower (2-4%) than at 130 ng/L 4-nonylphenol and in the control. At 4-nonylphenol concentrations of 750 ng/L only 23.8 +/- 1.2% of the larvae survived to the end of the yolk sac stage, at 280 ng/L 53.7 +/- 8.2%, at 130 ng/L 73.8 +/- 1.5%, and in the control 70.9 +/- 1.8%. Sperm motility was not affected by 4-nonylphenol as sperm motility rate, swimming velocity, swimming pattern and motility duration were similar in water and in water containing of 100, 250, or 750 ng/L 4-nonylphenol. Incubation of eggs in physiological saline solution containing of 100, 250, or 750 ng/L 4-nonylphenol did not change their fertilizability in comparison to the control. Therefore, 4-nonylphenol did not affect the egg viability. Also the fertilization process (sperm egg contact) was not influenced by 4-nonylphenol as the fertilization rate (percentage of hatched larvae) was similar to the control when eggs were fertilized in water containing of 100, 250, or 750 ng/L 4-nonylphenol.

/AQUATIC SPECIES/ Nonylphenol (NP) represents the most critical metabolite of alkylphenols (APs) and alkylphenol ethoxylates (APEs), non-ionic surfactants widely used in the formulation of domestic and industrial products. On the basis of in vitro and in vivo animal studies 4-nonylphenol (4-NP) is considered an endocrine disrupting chemical (EDC). The evidence to date indicates that mollusks are able to synthesize sex steroids from the precursor cholesterol and their endocrine pathways are theoretically susceptible to disruption. The aim of this study was to investigate the endocrine modulating potency of 4-NP in the freshwater mussel Dreissena polymorpha by looking at endogenous steroid levels in control and exposed individuals. 4-NP bioaccumulation in mussels tissues and alterations in the activity of enzymes related both to oxidative stress (catalase - CAT- and glutathione peroxidase - GPX-) and phase II metabolism (glutathione-S-transferase - GST-) were also assessed. The results highlighted a build-up of 4-NP in exposed mussels and an overall decrease of 17-beta-estradiol and testosterone levels. On the other hand this chemical at the tested concentrations does not interfere with the antioxidant defense mechanisms in D. polymorpha. The mechanisms by which 4-NP alter steroids levels are unknown and require more in-depth investigations.

/AQUATIC SPECIES/ Laboratory studies have suggested that some alkylphenols and pesticides elicit developmental toxicity to crustaceans. The purpose of the present study was to evaluate the possibility that the alkylphenol degradation product 4-nonylphenol is embryotoxic to the crustacean Daphnia magna through its known ability to interfere with the metabolic elimination of testosterone. Direct exposure of maternal daphnids to testosterone caused developmental abnormalities in neonates that consisted of partial arrest of early embryonic development and abnormalities in shell spine and first antennae development. Exposure of maternal daphnids to concentrations of 4-nonylphenol also produced developmental abnormalities though the profile of abnormalities was distinct from that observed throughout the testosterone concentration-response curve. Thus, 4-nonylphenol is a developmental toxicant in daphnids, but its toxicity is not consistent with that elicited by elevated testosterone accumulation. Further experiments demonstrated that testosterone was directly toxic to developing embryos, and the maternal organism can serve as the vector for this toxicity. In contrast, neither direct embryo exposure nor early maternal exposure to 4-nonylphenol elicited embryotoxicity consistent with that observed during continuous maternal and gestational exposure. Thus, 4-nonylphenol is not directly embryotoxic at these exposure levels, but rather toxicity is mediated by maternal influences during gestation. The threshold concentration for the occurrence of developmental abnormalities (approximately 44 ug/L) indicates that typical environmental concentrations of 4-nonylphenol pose no imminent hazard with respect to developmental toxicity. However, these effects do occur at sufficiently low levels to warrant evaluation of the relative susceptibility of other crustacean species to this previously uncharacterized mode of toxicity.

For more Ecotoxicity Excerpts (Complete) data for 4-Nonylphenol (40 total), please visit the HSDB record page.

4-Nonylphenol was detected at 239.6 ng/g lipid in herring gull (Larus argentatus) collected from Bohai Bay, China in Nov 2002(1). In the fur of 17 Baltic grey seals (Halichoerus grypus) collected 2014-2015 from the Baltic Sea and feathers of 26 herring gulls (Larus argentatus) collected 2010-2012 from the Gulf of Gdansk, 4-nonylphenol was detected at 5.5-91.3 and 4.9-151.3 ng/g dry weight, respectively(2).

The concentration of 4-nonylphenol in the liver of marine organisms collected 2007-2010 from Morro Bay, CA was as follows(1):[Table#5364]

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of July 27, 2017: http://actor.epa.gov/dashboard/]

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, exposure, and use to EPA as cited in the preamble in 51 FR 41329. Effective date: 3/29/96; Reporting date: 5/29/96.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. 4-Nonylphenol is included on this list. Effective date: 3/29/96; Sunset date: 6/30/98.

Alkylphenols are weak estrogenic environmental contaminants and have been implicated in the disruption of endocrine function in wildlife. The influence of biotransformation, tissue distribution, and elimination on biological activity was investigated in juvenile rainbow trout following a single iv dose of [(3)H]4-nonylphenol. Distribution and elimination of [(3)H]4-nonylphenol residues in tissues sampled 1, 2, 4, 24, 48, 72, and 144 hr after dosing was determined by sample combustion and liquid scintillation counting (LSC). Total 3H-labeled residue concentrations in trout 144 hr after dosing were in order: bile >> feces >> liver > pyloric caeca > kidney > brain, gill, gonad, heart, plasma, skeletal muscle, and skin. The depletion kinetics of [(3)H]residues from tissues and plasma was biphasic with prolonged beta-phase half-lives in muscle and liver of 99 hr. Radio-HPLC analysis of metabolites in bile, liver, pyloric caeca, and feces samples demonstrated similar profiles and contrasted with muscle where only parent compound was found. The predominant metabolite in bile was a glucuronide conjugate of 4-nonylphenol. Other metabolites included glucuronide conjugates of ring or side chain hydroxylated 4-nonylphenol. Liver contained a low level (1.7%) of covalently bound residues. Metabolism studies using isolated trout hepatocytes produced a similar range of metabolites and a sulfate conjugate of hydroxylated 4-nonylphenol. Despite rapid metabolism and excretion, a substantial depot of parent compound remained in muscle which will have implications for the maintenance of 4-nonylphenol residues and associated biological activity.

4-Nonylphenol (4-NP) is a well-known toxic environmental contaminant. The major objective of the present study was to identify reactive metabolites of 4-NP. Following incubations of 4-NP with NADPH- and GSH-supplemented human liver microsomes, 6 GSH conjugates, along with 19 oxidized metabolites, were detected by UPLC/Q-TOF mass spectrometry utilizing the mass defect filter method. Several authentic key metabolite standards were chemically synthesized for structural identification. Three GSH conjugates were found to derive from quinone methide intermediates, and the other three resulted from ortho-benzoquinone intermediates. Conjugation of the quinone methides with GSH produced benzylic-orientated GSH conjugates by 1,6-addition, while the reaction of the ortho-benzoquinone intermediates offered aromatic-orientated GSH conjugates. The conversion of 4-NP to the quinone methides and ortho-hydroquinones required cytochromes P450, specifically CYPs1A2, 2C19, 2D6, 2E1, and 3A4, while the oxidation of ortho-benzohydroquinones to the corresponding benzoquinones was apparently independent of microsomal enzymes. The ortho-benzoquinone derived from 4-NP was isomerized to the corresponding hydroxyquinone methide, and the former dominated the latter at a rate of approximately 20:1. The findings of the quinone methide and benzoquinone metabolites intensified the concern on the impact of 4-NP exposure on human health.

4-nonylphenol has known human metabolites that include (4-Nonylphenyl) hydrogen sulfate.

4-nonylphenol (4-NP) is an estrogenic endocrine active chemical that is present in detergents and is known to contaminate food and drinking water. The aim of the present study was to evaluate whether 4-NP crosses the human placenta and if so, to what extent. Human placentae obtained from healthy term singleton pregnancies were utilized in a dual ex-vivo re-circulating model of placental perfusion. Six placentae were perfused for 180 min following addition of 4-NP (30 ng/mL) to the maternal perfusate. Antipyrine and FITC dextran were used as positive and negative controls respectively to validate the integrity of the circuits. 4-NP was measured by High Performance Liquid Chromatography coupled with Fluorescence Detection (HPLC-FD). After 180 min of perfusion the transfer percentages for antipyrine and 4-NP were 25.6 +/- 1.4% (mean +/- s.e.m, n = 6) and 22.75 +/- 3.76% respectively and the transfer index for 4-NP was 0.8. We conclude that the intact form of 4-NP at environmentally relevant concentrations can transfer across the human placenta albeit at a slow rate.

Used with mixed-metal stabilizers for heat stabilization of plastics and to make phenolic resins; [HSDB]

Routinely used as a co-stabilizer with mixed-metal stabilizers for heat stabilization during plastic production

(1984) 7.34X10+10 g

(1993) 87,638,000 kg

p-Nonylphenol (PNP) is produced by the alkylation of phenol with nonene under acid catalysis. All commercially produced PNP is made from nonene based on the trimerization of propylene.

Reaction of nonene, branched with phenol by a Friedel Crafts alkylation, coproduced with dionylphenol. /Nonylphenol/

The two commercial purity grades of 4-nonylphenol are a technical grade which is composed of 10-12% 2-nonylphenol, 85-90% 4-nonylphenol, and up to 5% 2,4-dinonylphenol, and a high purity grade which contains 5% maximum 2-nonylphenol, 95% minimum 4-nonylphenol, and only a trace of 2,4-dinonylphenol.

Phenol, 4-nonyl-: ACTIVE

A mixture of isomeric monoalkylphenols, predominantly p-substituted /Nonylphenol/