2-Naphthol is a metabolite of naphthalene that is metabolized by CYP isoenzymes (CYP 1A1, CYP 1A2, CYP 2A1, CYP 2E1, and CYP 2F2). 2-Naphthol (10, 25, 50, and 100 μM) decreases the growth of peripheral blood mononuclear cells without causing cytotoxic effects [1].

Absorption, Distribution and Excretion
Between 5 and 10% of a cutaneous dose /of 2-naphthol/ has been recovered from the urine ... .

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Metabolism / Metabolites
Several pathways of drug metabolizing enzyme activity were measured in hepatic fractions of cattle, sheep, goats, chickens, turkeys, ducks, rabbits and rats. The pathways examined included the O-demethylation of p-nitrophenol, microsomal ester hydrolysis of procaine and glucuronidation of p-nitrophenol, and the cytosolic acetylation of sulfamethazine and sulfation of 2-naphthol. For most enzymatic pathways measured, goats were more similar to sheep (wether) than to cattle (steers). The exception was UDP-glucuronyltransferase activity, which was significantly higher for the goat than for any other species studied. Within the avian subset, the chicken and turkey were usually the most similar species. The activities of arylsulfotransferase isozymes III and IV were particularly low for the duck compared to the chicken and turkey. N-acetyltransferase activity was very high for rabbits and very low for sheep and goats.
Several pathways of drug metabolizing enzymic activity were measured in hepatic fractions of the channel catfish and rat using model substrates. The pathways examined included the O-demethylation of p-nitroanisole, microsomal ester hydrolysis of procaine and glucuronidation of p-nitrophenol and the cytosolic acetylation of sulfamethazine and sulfation of 2-naphthol. Catfish liver preparations were incubated at both 25 °C and 37 °C. The oxidative metabolism of p-nitrophenol was only 1/8 of that of the rat at 37 °C and 1/12 that of the rat at 25 °C. Procaine ester hydrolysis was negligible in catfish microsomal preparations. At 37 °C, p-nitrophenol glucuronidation was equivalent in catfish and rat microsomes. Catfish cytosolic preparations exhibited N-acetyltransferase and arylsulfotransferase nearly comparable to those of the rat. Rates of glucuronidation and sulfation were higher at 37 °C than at 25 °C in hepatic fractions of the catfish.
To characterize the substrate specificities of various isozymes of carboxylesterases, a series of carbonates, thiocarbonates, carbamates, and carboxylic acid esters containing alpha- or beta-naphthol or p-nitrophenol as leaving groups were tested as substrates of human, rat and mouse liver microsomal esterases; hydrolases A and B from rat liver microsomes were also tested. The carbonates, thiocarbonates, and carboxylic esters of alpha-naphthol were cleaved more rapidly than the corresponding beta-naphthol isomers by the mammalian liver esterases. The majority of the substrates was consistently hydrolyzed at higher rates by hydrolase B compared with hydrolase A. Compared with the corresponding carboxylates, the carbonate moiety of alpha- and beta-naphthol and p-nitrophenol lowered the specific activities of the enzymes by about 5 fold but improved stability under basic conditions. Human and mouse liver microsomal esterase activities were 5 orders of magnitude lower than the esterase activities of hydrolase B. The functional group and lipophilicity of the substrate structure influenced the activity of mammalian esterases.
The inhibition of hydroxysteroid-sulfotransferase (ST) activity in the rat liver by alkylamines was investigated. Liver homogenates were prepared from Wistar rats, and cytosolic fractions were obtained. ST activities towards dehydroepiandrosterone (DHEA), androsterone (AS), and 2-naphthol (2NA) were assayed. Cytosolic fractions were fractionated by column chromatography. Triethylamine, which was used as an elution solvent for column chromatography to purify chemically synthesized 3-phosphoadenosine-5-phosphosulfate (PAPS) inhibited androgen sulfation with AS and DHEA, but did not affect ST activities with cortisol and 2-NA. The sulfate donor ability of various PAPS preparations were compared. Fourteen primary, secondary, and tertiary amines were examined for inhibitory actions on ST activities towards DHEA, cortisol, and 2-NA. A secondary amine, di-n-butylamine, and three tertiary amines, triethylamine, tri-n-propylamine and tri-n-butylamine, inhibited DHEA ST activity by 40 to 60%, irrespective of sex. However, 2-NA and cortisol ST activities were not affected to any significant extent. Lineweaver Burk plots with partially purified hydroxysteroid ST indicated that the inhibition by triethylamine fitted a noncompetitive inhibition. The /results/ conclude that glucocorticoid ST appears to be distinct from the hydroxysteroid ST, and that this has implications for the inhibition of human liver ST activities by synthetic steroids and tertiary amines given as drugs.
For more Metabolism/Metabolites (Complete) data for 2-NAPHTHOL (8 total), please visit the HSDB record page.
2-Naphthol is a known human metabolite of naphthalene.

Toxicity Summary
IDENTIFICATION AND USE: 2- Naphthol is a white, bulky leaflets or white powder with faint phenol-like odor. The principal uses for 2-naphthol are in the dyes and pigments industries, eg, as a coupling component for azo dyes, and to make important intermediates, such as 3-hydroxy-2-naphthalenecarboxylic acid (BON) and its anilide (naphthol AS), 2-naphtholsulfonic acids, aminonaphtholsulfonic acids, and 1-nitroso-2-naphthol. The major pharmaceutical products based on 2-naphthol are the antifungal tolnaftate, produced by reaction with thiophosgene and N-methyl-m-toluidine; the semisynthetic penicillin nafcillin, produced via 2-ethoxynaphthalene; and the anti-inflammatory naproxen, produced via 2-methoxynaphthalene. It is also was used as a counterirritant in alopecia, also as an anthelmintic, and as an antiseptic in treatment of scabies. HUMAN EXPOSURE AND TOXICITY: The extensive application of 2-naphthol ointments has been responsible for systemic side effects, including vomiting and death. Ingestion can produce renal damage, vomiting, diarrhea, abdominal pain, syncope, convulsions, and hemolytic anemia. Twenty patients who were treated for scabies by rubbing 50 g of a salve containing 7.5% 2-naphthol over the whole body morning and evening for 2 days were reported to have developed hyperemia of the fundus and many had very small white and pigmented spots in the retina. Vitreous opacities were noticed in two cases. Only in one case was abnormality of the lens observed, and this was only a dot in the posterior cortex. Visual acuity was reported to be impaired in two cases, but neither of these had normal eyes before the treatment. ANIMAL STUDIES: Experimentally in rabbits the most consistent ocular change induced by admin 2-naphthol either by stomach or by application to the skin was a development in the retina of small white shiny flecks which soon became pigmented. These became more numerous and increased in size as daily admin of the chemical continued. The retinal vessels and the iris commonly became hyperemic. The aqueous was sometimes slightly turbid, and the vitreous commonly became turbid early, but then cleared despite continuing admin of naphthol. The cornea and conjunctiva were never involved. The other study reported that in the retinas of poisoned adult rabbits spotty degeneration of the rods and cones and irregular variation in the amt of pigment in the pigment epithelium were observed. Vacuoles were present in the nuclear and nerve fiber layer and the ciliary epithelium. When 2-naphthol was administered to pregnant rabbits, the offspring had congenital cataracts, degeneration of the neuroepithelium, and hypertrophy of the retinal pigment cells. An in vivo study was conducted of the biochemical pathways modulating the cataractogenicity of naphthalene. Male mice were treated with naphthalene or its metabolites and with various chemical probes that modulate critical biochemical pathways relevant to naphthalene bioactivation and detoxification. No cataractogenic or lethal effects from 2-naphthol were noted at dose levels of 56 or 100 mg/kg; however doses of 177 and 562 mg/kg killed all the animals within 1.5 hr. ECOTOXICITY STUDIES: As test systems, fish embryos and larvae were the most sensitive, juvenile fathead minnows and arthropods had intermediate sensitivity and algae and snails were the most resistant to the test compounds.

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Toxicity Data
LC50 (rat) = 2,200 mg/m3/4h

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Non-Human Toxicity Values
LD50 Mouse ip 97,500 mg/kg
LD50 Rat oral 1960 mg/kg

[1]. Determination of cytotoxic and genotoxic effects of naphthalene, 1-naphthol and 2-naphthol on human lymphocyte culture. Toxicol Ind Health. 2014 Feb;30(1):82-9.

2-naphthol is a naphthol carrying a hydroxy group at position 2. It has a role as an antinematodal drug, a genotoxin, a human xenobiotic metabolite, a mouse metabolite, a human urinary metabolite and a radical scavenger.
2-Naphthol is a colorless crystalline solid and an isomer of 1-naphthol, differing by the location of the hydroxyl group on naphthalene. The naphthols are naphthalene homologues of phenol, with the hydroxyl group being more reactive than in the phenols. 2-Naphthol has several different uses including dyes, pigments, fats, oils, insecticides, pharmaceuticals, perfumes, antiseptics, synthesis of fungicides, and antioxidants for rubber. Detection of 2-Naphthol in urine usually results from long-term persistent exposure to pesticides such as chlorpyrifos, but also due to exposure to naphthalene in older types of mothballs, fires that produce polyaromatic hydrocarbons (PAHs), and tobacco smoke.

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Therapeutic Uses
2-Naphthol ... has had medical uses as a counterirritant in alopecia, also as an anthelmintic, and as an antiseptic in treatment of scabies.

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Drug Warnings
2-Naphthol-containing pastes should be applied only for short periods of time and to a limited area not exceeding 150 square cm.

144.057

135-19-3

2-Naphthol-d8;78832-61-8;2-Naphthol-d7;78832-54-9

8663

Off-white to light brown solid powder

1.2±0.1 g/cm3

285.5±0.0 °C at 760 mmHg

120-122 °C(lit.)

144.0±10.6 °C

0.0±0.6 mmHg at 25°C

1.678

2.71

1

1

0

11

133

0

O([H])C1C([H])=C([H])C2=C([H])C([H])=C([H])C([H])=C2C=1[H]

JWAZRIHNYRIHIV-UHFFFAOYSA-N

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

naphthalen-2-ol

NSC 2044 NSC-2044Betanaphthol NSC2044

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

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

Solubility in Formulation 1: ≥ 2.5 mg/mL (17.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (17.34 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (17.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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