1-Naphthol targets multiple enzymes and pathways. It acts as a cholinesterase (acetylcholinesterase) inhibitor. It also inhibits 5-lipoxygenase in rat basophilic leukemia cells, prostaglandin G/H synthase in BSV cell lines, and exhibits activity against the androgen receptor (AR) pathway and estrogen receptor (ER) activity models.

In vitro, 1-Naphthol exhibits a range of bioactivities. It inhibits 5-lipoxygenase in rat basophilic leukemia cells with an IC50 of 3600 nM and prostaglandin G/H synthase in BSV cell lines with an IC50 of 2000 nM. It also demonstrates significant inhibition of mouse arachidonic acid-induced ear edema by 59% at a dose of 100 μg/ear.

In vivo, 1-Naphthol has been studied for its anti-inflammatory effects. It significantly inhibits arachidonic acid-induced ear edema in mice, demonstrating its potential as an anti-inflammatory agent. As a metabolite of carbaryl and naphthalene, its presence in vivo is linked to the metabolism of these xenobiotics.

The in vitro enzyme inhibition assay for 1-Naphthol involves incubating the compound with the target enzyme (e.g., 5-lipoxygenase, prostaglandin G/H synthase, or acetylcholinesterase) and a specific substrate. The enzyme activity is measured by detecting the reaction product using spectrophotometry or fluorometry, and the IC50 value is calculated from the inhibition curve.

In vitro cell culture studies for 1-Naphthol utilize various cell lines, such as rat basophilic leukemia cells, to assess its inhibitory effects on enzymes like 5-lipoxygenase. Cells are treated with the compound, and the production of inflammatory mediators or enzyme activity is measured. Its role as a fluorescent probe is also studied in cell-based systems to monitor micellar aggregation and sol-gel transitions.

In vivo animal experiments for 1-Naphthol include the mouse arachidonic acid-induced ear edema model. In this model, the compound is topically applied to the mouse ear, and the reduction in edema is measured as an indicator of anti-inflammatory activity. Its role as a metabolite is studied in animal models of xenobiotic metabolism.

Absorption, Distribution and Excretion
Following topical application of ((14)C)naphthyl-1-ol, urinary excretion of (14)C indicated that approximately 50% of (14)C was absorbed dermally. Sixty-two workers at a carbonization plant were examined and exposed to benzene, naphthalene, toluene, o-xylene, p-xylene, phenol, and pyridine. Significant differences were found in the concentrations of phenol (21.7–97.6 mg/L), 1-naphthol (0.1–9.38 mg/L), hippuric acid (95.5–873.9 mg/L), and m-methylhippuric acid (29.0–93.5 mg/L) in urine samples collected before and after occupational exposure. A correlation was found between benzene and naphthalene in the breathing zone air of the coking plant workers and phenol and 1-naphthol in their urine.
The chemical exposure of an assembly worker handling creosote-impregnated wood and a worker removing coal tar pitch was assessed by measuring the concentrations of naphthalene and various polycyclic aromatic hydrocarbons (PAHs) in the air, as well as the excretion of 1-naphthol and 1-pyrene in urine. During coal tar pitch removal, the total concentration of PAHs and the total concentration of PAHs containing 4–6 aromatic rings were higher, at 440 μg/m³ and 290 μg/m³, respectively. The PAH concentration in the assembly worker's workplace was approximately 1/50th of this value. The concentration of naphthalene in the air was the opposite (assembly worker: 1000 μg/m³; coal tar pitch removal worker: 160 μg/m³). Correspondingly, the concentration of 1-naphthol in the urine of the assembly worker was 15–20 times higher than that of the worker removing coal tar pitch. The concentration of 1-pyrene in the urine of the worker removing coal tar pitch was 2–4 times higher than that of the assembly worker. Since the estimated dose of pyrene inhaled by the assembler accounts for only 2%-25% of the pyrene excreted in urine over 24 hours, the skin is presumed to be the primary route of absorption. …
In male mice, 95% of the administered dose of α-naphthol was eliminated within 72 hours after oral administration of 45 mg/kg body weight.

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Metabolism/Metabolites
1-Naphthyl-α-D-glucoside is produced in blowflies and maggots…1-Naphthyl phosphate is produced in fruit flies and maggots. /Excerpt from Table/
1-Naphthyl-β-D-glucuronide is produced in rats, rabbits, fruit flies, and mice. /Excerpt from Table/
1-Naphthyl sulfate is produced in rats, rabbits, mice, guinea pigs, fruit flies, and maggots. /Excerpt from Table/
After injection of 0.1 mmol 1-naphthol into the intestinal loop (in vivo rat experiment), 70-90% of the 1-naphthol in the intestinal venous blood is present as 1-naphthol glucuronide. For injection doses of 1.0 and 2.0 mmol, the proportion of 1-naphthol present as 1-naphthol glucuronide is 25-50%.
For more complete metabolite/metabolite data on 1-naphthol (a total of 8 metabolites), please visit the HSDB record page.
Known metabolites of 1-naphthol include 1-naphthyl glucuronide.
1-Naphthol is a known metabolite of naphthalene.
Phospoxase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate certain organophosphates through hydrolysis. PON1 hydrolyzes active metabolites in a variety of organophosphate pesticides and nerve agents (such as soman, sarin, and VX). The presence of PON1 polymorphism leads to differences in the enzyme level and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effects of organophosphate exposure.
1-Naphthol has a molecular formula of C10H8O and a molecular weight of 144.17 g/mol. It is a solid compound that is slightly soluble in water and soluble in organic solvents. As a fluorescent probe, its photophysical properties are utilized to study microenvironmental changes. It is typically stored at room temperature, protected from light.

Toxicity Summary
1-Naphthol is a cholinesterase, or acetylcholinesterase (AChE) inhibitor. Cholinesterase inhibitors (or "anticholinesterases") inhibit the activity of acetylcholinesterase. Because acetylcholinesterase has important physiological functions, chemicals that interfere with its activity are potent neurotoxins; even low doses can cause excessive salivation and lacrimation, followed by muscle spasms, ultimately leading to death. Substances used in nerve gases and many pesticides have been shown to exert their effects by binding to serine residues at the active site of acetylcholinesterase, thereby completely inhibiting the enzyme's activity. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, which is released at the neuromuscular junction, causing muscle or organ relaxation. Inhibition of acetylcholinesterase results in the accumulation and sustained action of acetylcholine, leading to the continuous transmission of nerve impulses and the inability to stop muscle contractions. The most common acetylcholinesterase inhibitors are phosphorus-containing compounds, which are designed to bind to the enzyme's active site. Its structural requirements include a phosphorus atom with two lipophilic groups, a leaving group (e.g., a halide or thiocyanate), and a terminal oxygen atom.

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Toxicity Data
LC50 (Rat)> 420 mg/m³/1h

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Interactions
…This paper investigates the potential for substituted aryl compounds aniline, 1-naphthylamine, and 1-naphthol (1-NOH) to react with hypochlorous acid (HOCl) and transform into genotoxic products, using these as model xenobiotics. The compounds were first exposed to hypochlorous acid (HOCl, 25–150 μM) in phosphate buffer, followed by treatment of human fibroblasts or purified DNA. Intracellular DNA single-strand breaks and the binding of the HOCl reaction product 1-[14C]NOH to purified DNA were assessed using DNA alkaline elution and scintillation counting methods, respectively. The results showed that neither HOCl nor the compounds themselves could damage cellular DNA. However, the HOCl reaction product could produce DNA breaks up to 400 rad equivalent. The HOCl reaction products of aniline and model bicyclic aryl compounds exhibit different DNA breakage characteristics. The HOCl reaction product 1-[14C]NOH is stable and binds to DNA up to 124 pmol/mg DNA. Sodium thiosulfate, glutathione, and taurine all inhibit the transformation reaction; however, only the former two can block the binding of the HOCl reaction product 1-NOH to DNA. UV spectroscopy showed that HOCl reacts rapidly (<1 min) with 1-NOH at pH 7.2 or pH 5.0 in vivo, with the same reaction effect. In this study, the reaction concentration of HOCl was 2 to 11 times lower than the concentration produced by stimulated neutrophils in vitro. These results indicate that some aryl compounds can react rapidly with near physiological concentrations of hypochlorous acid (-OCl) to form relatively long-lived products that can bind to DNA and are genotoxic to human cells.

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Non-human toxicity values
Rats oral LD50: 2.59 g/kg
Cats oral LD50: 134 mg/kg body weight
Mice oral LD50: 275 mg/kg body weight
Rabbit skin LD50: >10,000 mg/kg /Data from table/
For more non-human toxicity values (complete data) for 1-naphthol (8 types in total), please visit the HSDB record page.
Toxicological data indicate that 1-Naphthol, as a metabolite of naphthalene, can be a skin irritant. It is also a potential environmental pollutant. Its toxicity is primarily associated with its role as a metabolic intermediate and its reactivity. It is classified as a research compound and is not intended for human therapeutic use.

[1]. 1-Naphthol as an ESPT fluorescent molecular probe for sensing thermotropic microenvironmental changes of pluronic F127 in aqueous media. Phys Chem Chem Phys. 2015 Jul 14;17(26):16752-9.

1-Naphthol is a naphthol with a hydroxyl group at the 1-position. It is a genotoxin and a metabolite of exogenous substances in humans. 1-Naphthol has been reported in Selaginella sinensis, Juglans nigra, and Magnolia liliiflora, with relevant data available. 1-Naphthol (1N) is a metabolite of carbaryl and naphthalene, and an intermediate in the metabolism of exogenous substances by cytochrome P450. It is spontaneously generated from (1R,2S)-naphthalene epoxide, which is then converted to 1,4-dihydroxynaphthol. Although 1-Naphthol is not persistent in vivo, a single urine sample is sufficient to predict exposure to the broad-spectrum organophosphate pesticide chlorpyrifos over several months. In adult men, TCPY and 1N are associated with decreased testosterone levels (A3198, A3199).

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Mechanism of Action
This study investigated the toxic mechanisms of 1-naphthol and its two possible metabolites, 1,2-naphthoquinone and 1,4-naphthoquinone, on freshly isolated rat hepatocytes. Both 1-naphthol and the two naphthoquinones exhibited dose-dependent hepatotoxicity. [1-14C]-1-naphthol is primarily metabolized in hepatocytes to glucuronic acid and sulfate conjugates, but small amounts of covalently bound products are also generated. Exposure to 1-naphthol and naphthoquinones resulted in vesicular protrusions on the hepatocyte surface, along with a dose-dependent decrease in intracellular glutathione (GSH) levels, which preceded the onset of cytotoxicity. Dicoumarol (a DT-dihydroflavinase (NAD(P)H: quinone oxidoreductase) inhibitor) enhanced the toxicity of 1-naphthol and naphthoquinones.
This enhanced toxicity is accompanied by more surface vesicular protrusions, increased intracellular GSH consumption (especially in the case of 1-naphthol and 1,4-naphthoquinone), and reduced metabolism of 1-naphthol to its conjugates, while the amount of covalently bound products is affected to varying degrees. These results support the idea that the toxicity of 1-naphthol may be mediated by the formation of 1,2-naphthoquinone and/or 1,4-naphthoquinone, which may subsequently be metabolized into naphthymenone radicals via single-electron reductive metabolism. These radicals, in turn, may covalently bind to important cellular macromolecules or enter the redox cycle with molecular oxygen, thereby generating reactive oxygen species. Both processes appear to play a role in the cytotoxic effects of 1-naphthol.

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Therapeutic Use
Compared to the corresponding normal colon tissue surgically resected and maintained in short-term organ culture, 1-naphthol exhibits selective toxicity to human colorectal tumors. Of the 24 tumors studied, 19 showed significantly differential responses. In the short-term organ culture system, three human colonic adenocarcinoma xenografts responded to 1-naphthol in the same way as the surgically resected primary tumors. 1-Naphthol, 1,2-naphthoquinone, and 1,4-naphthoquinone also exhibit toxicity against two human colon adenocarcinoma cell lines, LoVo and COLO 206. The selective toxicity of 1-naphthol is partly due to its impaired binding ability to tumor cells, leading to its accumulation in tumor tissue. Higher concentrations of 1-naphthol may exert toxic effects directly or through the formation of naphthoquinones. Some indirect evidence suggests that 1,2-naphthoquinone or 1,4-naphthoquinone may be involved in the cytotoxicity of 1-naphthol. Our study indicates the need for further investigation into the potential use of 1-naphthol or related compounds as antitumor drugs.
1-Naphthol is a research compound with no clinical approval. It is widely used as a fluorescent molecular probe to study hydrophobic domains and sol-gel transitions. It also serves as a reference standard for studying the metabolism of naphthalene and carbaryl. Its inhibitory effects on various enzymes make it a useful tool in biochemical research.

C10H8O

144.1699

144.057

90-15-3

1-Naphthol-d8;207569-03-7

7005

White to off-white solid powder

1.2±0.1 g/cm3

288.0±0.0 °C at 760 mmHg

94-98ºC

144.0±10.6 °C

0.0±0.6 mmHg at 25°C

1.678

2.71

1

1

0

11

133

0

KJCVRFUGPWSIIH-UHFFFAOYSA-N

InChI=1S/C10H8O/c11-10-7-3-5-8-4-1-2-6-9(8)10/h1-7,11H

naphthalen-1-ol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol : ~100 mg/mL (~693.63 mM)
H2O : ~1 mg/mL (~6.94 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)