4-NONYLPHENOL

4-nonylphenol is a member of the class of phenols that is phenol which is para-substituted with a nonyl group.
 
4-nonylphenol (4-NP) is an estrogenic endocrine active chemical that is present in detergents and is known to contaminate food and drinking water. 

Nonylphenol is an organic compound of the wider family of alkylphenols.

4-nonylphenol has a role as an environmental contaminant. Environmental pollutant arising from the degradation of nonionic surfactants in sewage Nonoxynol-9, one of the APEs, is used as a surfactant in cleaning and cosmetic products, and as a spermicide in contraceptives. 

4-nonylphenol is a product of industrial synthesis formed during the alkylation process of phenols, particularly in the synthesis of polyethoxylate detergents.

CAS Number: 104-40-5
EC Number: 203-199-4
Molecular Formula: C15H24O
Molecular Weight: 220.35 g/mol
Boiling point: 290-300°C
Melting point: -8°C
Relative density (water = 1): 0.95 (20°C)
Solubility in water, g/100ml at 25°C: 0.06 (very poor)
Vapour pressure, Pa at 25°C: 0,3
Relative vapour density (air = 1): 7.59
Relative density of the vapour/air-mixture at 20°C (air = 1): 1.05
Flash point: 141-155°C c.c.
Auto-ignition temperature: 370°C
Octanol/water partition coefficient as log Pow: 4.48  

SYNONYMS: 4-nonylphenol, 104-40-5, 4-n-Nonylphenol, p-Nonylphenol, 4-nonyl phenol, para-Nonylphenol, Phenol, 4-nonyl-, p-n-Nonylphenol, Phenol, p-nonyl-, para Nonyl phenol, p-n-Nonylphenol, 4-Nonyl-Phenol, 4-n-Nonyl phenol, DTXSID5033836, MFCD00002396, CHEBI:34440, 68081-86-7, 4-NP, DTXCID001857, 4-tert-nonylphenol, CAS-104-40-5, CCRIS 1251, HSDB 5359, EINECS 203-199-4, UNII-I03GBV4WEL, BRN 2047450, nonyl-phenol, p-nonyl phenol, p-nonyl-phenol, Para-nonyl phenol, 4-Nonylphenol, tech., Spectrum_001973, SpecPlus_000624, P-NONYLPHENOL (ENDOCRINE DISRUPTER), Spectrum2_001832, Spectrum3_000872, Spectrum4_000712, Spectrum5_002066, 4-n-Nonylphenol, 85%, 4-n-Nonylphenol, 98%, I03GBV4WEL, BIDD:PXR0002, SCHEMBL15887, BSPBio_002543, KBioGR_001263, KBioSS_002539, SPECTRUM330085, 3-06-00-02067 (Beilstein Handbook Reference), BIDD:ER0006, DivK1c_006720, SPBio_001903, CHEMBL153062, KBio1_001664, KBio2_002530, KBio2_005098, KBio2_007666, KBio3_002043, 4-Nonylphenol, analytical standard, Tox21_201241, Tox21_303647, BDBM50410532, CCG-39613, LMPK15010001, STL453644, AKOS015888197, NCGC00090918-01, NCGC00090918-02, NCGC00090918-03, NCGC00090918-05, NCGC00090918-06, NCGC00090918-07, NCGC00090918-08, NCGC00257420-01, NCGC00258793-01, PD002549, 1ST001668, NS00010283, 4-n-Nonylphenol 10 microg/mL in Acetonitrile, 4-n-Nonylphenol 10 microg/mL in Cyclohexane, 4-n-Nonylphenol 100 microg/mL in Cyclohexane, G83718, 4-Nonylphenol, PESTANAL(R), analytical standard, SR-05000002459, J-001167, Q4545806, SR-05000002459-1, 4-Nonylphenol, certified reference material, TraceCERT(R).

Because of their man-made origins, nonylphenols are classified as xenobiotics. In nonylphenols, a hydrocarbon chain of nine carbon atoms is attached to the phenol ring in either the ortho (2), meta (3), or para (4) position, with the most common ring isomers being ortho or para. Moreover, the alkyl chains can exist as either linear n-alkyl chains, or complex branched chains. Nonylphenol is commonly obtained as a mixture of isomers, and is thus usually found as a pale yellow liquid at room temperature with a freezing point of -10°C and a boiling point of 295-320°C. However, pure isomers of nonylphenol crystallize readily at room temperatures and for example, para-n-nonylphenol, forms white crystals at room temperature. Nonylphenol, and a related compound tert-octylphenol, were first detected as an air pollutant in New York City and New Jersey, probably due to its evaporation from the Hudson river and other smaller rivers in the region that routinely receive municipal wastewaters. It is possible that the atmosphere is a destructive sink for nonylphenol as it is probably reactive with atmospheric radicals and/or is photoactive.

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). 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.

Nonylphenols are a family of closely related organic compounds composed of phenol bearing a 9 carbon-tail. Nonylphenols can come in numerous structures, all of which may be considered alkylphenols. Nonylphenols are used in manufacturing antioxidants, lubricating oil additives, laundry and dish detergents, emulsifiers, and solubilizers. Nonylphenols are used extensively in epoxy formulation in North America but its use has been phased out in Europe. Nonylphenols are also precursors to the commercially important non-ionic surfactants alkylphenol ethoxylates and nonylphenol ethoxylates, which are used in detergents, paints, pesticides, personal care products, and plastics. Nonylphenol has attracted attention due to its prevalence in the environment and its potential role as an endocrine disruptor and xenoestrogen, due to its ability to act with estrogen-like activity. The estrogenicity and biodegradation heavily depends on the branching of the nonyl sidechain. Nonylphenol has been found to act as an agonist of the GPER (GPR30).

Nonylphenols fall into the general chemical category of alkylphenols. The structure of NPs may vary. The nonyl group can be attached to the phenol ring at various locations, usually the 4- and, to lesser extent, the 2-positions, and can be either branched or linear. A branched nonylphenol, 4-nonylphenol, is the most widely produced and marketed nonylphenol. The mixture of nonylphenol isomers is a pale yellow liquid, although the pure compounds are colorless. The nonylphenols are moderately soluble in water but soluble in alcohol.

Nonylphenol arises from the environmental degradation of nonylphenol ethoxylates, which are the metabolites of commercial detergents called alkylphenol ethoxylates. NPEs are a clear to light orange color liquid. Nonylphenol ethoxylates are nonionic in water, which means that they have no charge. Because of this property they are used as detergents, cleaners, emulsifiers, and a variety of other applications. They are amphipathic, meaning they have both hydrophilic and hydrophobic properties, which allows them to surround non-polar substances like oil and grease, isolating them from water.

Nonylphenol can be produced industrially, naturally, and by the environmental degradation of alkylphenol ethoxylates. Industrially, nonylphenols are produced by the acid-catalyzed alkylation of phenol with a mixture of nonenes. This synthesis leads to a very complex mixture with diverse nonylphenols. Theoretically there are 211 constitutional isomers and this number rise to 550 isomers if we take the enantiomers into account. To make NPEs, manufacturers treat NP with ethylene oxide under basic conditions. Since its discovery in 1940, nonylphenol production has increased exponentially, and between 100 and 500 million pounds of nonylphenol are produced globally every year, meeting the definition of High Production Volume Chemicals.

Nonylphenols are also produced naturally in the environment. One organism, the velvet worm, produces nonylphenol as a component of its defensive slime. The nonylphenol coats the ejection channel of the slime, stopping it from sticking to the organism when it is secreted. Nonylphenol also prolongs the drying process long enough for the slime to reach its target.

Nonylphenol is used in manufacturing antioxidants, lubricating oil additives, laundry and dish detergents, emulsifiers, and solubilizers. It can also be used to produce tris(4-nonyl-phenyl) phosphite (TNPP), which is an antioxidant used to protect polymers, such as rubber, Vinyl polymers, polyolefins, and polystyrenics in addition to being a stabilizer in plastic food packaging. Barium and calcium salts of nonylphenol are also used as heat stabilizers for polyvinyl chloride (PVC). Nonylphenol is also often used an intermediate in the manufacture of the non-ionic surfactants nonylphenol ethoxylates, which are used in detergents, paints, pesticides, personal care products, and plastics. Nonylphenol and nonylphenol ethoxylates are only used as components of household detergents outside of Europe. Nonyl Phenol, is used in many epoxy formulations mainly in North America.

Nonylphenol persists in aquatic environments and is moderately bioaccumulative. Nonylphenol is not readily biodegradable, and it can take months or longer to degrade in surface waters, soils, and sediments. Nonbiological degradation is negligible. Nonylphenol is partially removed during municipal wastewater treatment due to sorption to suspended solids and biotransformation. Many products that contain nonylphenol have "down-the-drain" applications, such as laundry and dish soap, so the contaminants are frequently introduced into the water supply. In sewage treatment plants, nonylphenol ethoxylate degrades into nonylphenol, which is found in river water and sediments as well as soil and groundwater. Nonylphenol photodegrades in sunlight, but its half-life in sediment is estimated to be more than 60 years. Although the concentration of nonylphenol in the environment is decreasing, it is still found at concentrations of 4.1 μg/L in river waters and 1 mg/kg in sediments.

A major concern is that contaminated sewage sludge is frequently recycled onto agricultural land. The degradation of nonylphenol in soil depends on oxygen availability and other components in the soil. Mobility of nonylphenol in soil is low.

Bioaccumulation is significant in water-dwelling organisms and birds, and nonylphenol has been found in internal organs of certain animals at concentrations of 10 to 1,000 times greater than the surrounding environment. Due to this bioaccumulation and persistence of nonylphenol, it has been suggested that nonylphenol could be transported over long distances and have a global reach that stretches far from the site of contamination.

Nonylphenol is not persistent in air, as it is rapidly degraded by hydroxyl radicals.

The production and use of nonylphenol and nonylphenol ethoxylates is prohibited for certain situations in the European Union due to its effects on health and the environment. In Europe, due to environmental concerns, they also have been replaced by more expensive alcohol ethoxylates, which are less problematic for the environment due to their ability to degrade more quickly than nonylphenols. The European Union has also included NP on the list of priority hazardous substances for surface water in the Water Framework Directive. They are now implementing a drastic reduction policy of NP's in surface waterways. The Environmental quality standard for NP was proposed to be 0.3 ug/L. In 2013 nonylphenols were registered on the REACH candidate list.

In the US, the EPA set criteria which recommends that nonylphenol concentration should not exceed 6.6 ug/L in fresh water and 1.7 ug/L in saltwater. In order to do so, the EPA is supporting and encouraging a voluntary phase-out of nonylphenol in industrial laundry detergents. Similarly, the EPA is documenting proposals for a "significant new use" rule, which would require companies to contact the EPA if they decided to add nonylphenol to any new cleaning and detergent products. They also plan to do more risk assessments to ascertain the effects of nonylphenol on human health and the environment.

In other Asian and South American countries nonylphenol is still widely available in commercial detergents, and there is little regulation.

Nonylphenol is registered under the REACH Regulation and is manufactured in and / or imported to the European Economic Area, at ≥ 1 to < 10 tonnes per annum.

Nonylphenol is used by professional workers (widespread uses), in formulation or re-packing, at industrial sites and in manufacturing.

Nonylphenol is used in the following products: coating products.
Other release to the environment of this substance is likely to occur from: indoor use as processing aid and outdoor use as processing aid.

Nonylphenol is used in the following products: coating products, fillers, putties, plasters, modelling clay and inks and toners.
Release to the environment of this substance can occur from industrial use: formulation of mixtures.

4-Nonylphenol (4-NP) is an organic compound widely utilized across industrial and commercial sectors owing to its affordability and abundant availability. Functioning as a nonionic surfactant, it is a commonplace ingredient in detergents, cleaners, and personal care products. Although the precise mechanism of action remains incompletely understood, it is recognized that 4-nonylphenol interacts with various hormones and receptors. Furthermore, 4-Nonylphenol has been observed to interact with nuclear receptors, proteins that selectively bind to molecules and regulate gene expression.

Nonylphenol is used in the production of synthetics, stabilisers, as well as phenolic and epoxide-resins. The major part, however, is used in nonylphenol ethoxylate production.

Nonylphenol ethoxylate is water soluble and used as surfactant, e.g., in industrial cleaners. Further applications include those as emulsifiers, e.g., in paints and lacquers, adhesives and pesticides.
In the environment, nonylphenol ethoxylate is successively degraded to nonylphenol.

Degradation of nonylphenol is rather slow. It is far more toxic than the parent compound and has a high potential for bioaccumulation. Furthermore, nonylphenol is an endocrine disruptor with estrogenic activity.

Of all nonylphenol ethoxylates, the 4-nonylphenol-compounds are commercially most important. Accordingly, their degradation products - i.e., linear and branched 4-nonylphenol - are widely found in the environment.

Since 2003, certain applications of nonylphenol ethoxylate which may lead to high emissions are restricted or banned in the EU.

Combustible material: may burn but does not ignite readily. When heated, vapors may form explosive mixtures with air: indoors, outdoors and sewers explosion hazards. Those substances designated with a (P) may polymerize explosively when heated or involved in a fire. Corrosives in contact with metals may evolve flammable hydrogen gas. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form.

Health Hazard
Moderately toxic if swallowed. Severely irritating to skin and eyes.

Reactivity Profile
NONYLPHENOL behaves as a very weak organic acid. Incompatible with strong reducing substances such as hydrides, nitrides, alkali metals, and sulfides. Flammable gas (H2) is often generated, and the heat of the reaction may ignite the gas. Likely to react exothermically with concentrated sulfuric acid and nitric acid.