Alpha-Naphthylthiourea

log Kow = 1.65

1.66 (calculated)

1.66

Specific Gravity (water= 1): Greater than 1

>1 g/cm³

Prisms from alcohol

Colorless ... solid

White, crystalline or gray powder

0.06 % (NIOSH, 2024)

In water, 600 mg/L at 25 °C

Solubility in acetone = 2.43 g/100 mL; in triethylene glycol = 8.6 g/100 mL; fairly soluble in hot alcohol

Slightly soluble in ethanol, ethyl ether, acetone

Very slightly soluble in most organic solvents

Solubility in water: none

Decomposes (NIOSH, 2024)

400 °C @760 [mm Hg]

Decomposes

Hazardous decomposition products include: sulfur dioxide, oxides of nitrogen, and carbon monoxide.

When heated to decomp ...it emits toxic fumes of /nitrogen oxides and sulfur oxides./

388 °F (EPA, 1998)

198 °C

198 °C

198 °C

388 °F

Danger

H300: Fatal if swallowed [Danger Acute toxicity, oral]

P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501 (click each P-code to see the statement)

Danger

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501 (click each P-code to see the statement)

Poison

Poison

Emits sulfur dioxide, oxides of nitrogen, and carbon monoxide fumes upon decomposition. It reacts with silver nitrate and strong oxidizers. Avoid decomposing heat. (EPA, 1998)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

· Combustible material: may burn but does not ignite readily.

Combustible under specific conditions. Gives off irritating or toxic fumes (or gases) in a fire.

Moderately toxic: probable oral lethal dose (human) 0.5-5 gm/kg, or between 1 ounce and 1 pint (or l lb.) for 150 lb. person. Chronic sublethal exposure may cause antithyroid activity. Can produce hyperglycemia of three times normal in three hours. People with chronic respiratory disease or liver disease may be especially at risk. (EPA, 1998)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

· TOXIC and/or CORROSIVE; inhalation, ingestion or skin contact with material may cause severe injury or death.

The lethal oral dose in humans is about 4 g/kg; TLV based on thyroid effects and nausea; In high-dose feeding and intraperitoneal injection studies, animals develop liver injury, pleural and pericardial effusions, and pulmonary edema. [ACGIH]

1651 153

1651 153

Amides and Imides

Amides and Imides

Harris WF; Curr Vet Ther 6: 117-9 (1977). A review with 2 references of the mechanism of ANTU toxicity, poisoning, & its treatment.

Boyd MR; CRC Crit Rev Toxicol 7 (2): 103-76 (1980). An extensive review of the in vivo biotransformation is presented.

P072; As stipulated in 40 CFR 261.33, when alpha-naphthylthiourea, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

Stay upwind, and out of low areas. Wear self-contained breathing apparatus and full protective clothing.

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

Use water spray, powder, foam, carbon dioxide.

Fresh air, rest. Half-upright position. Artificial respiration may be needed. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Give a slurry of activated charcoal in water to drink. Induce vomiting (ONLY IN CONSCIOUS PERSONS!). Refer for medical attention .

· CALL 911. Then call emergency response telephone number on shipping paper. If shipping paper not available or no answer, refer to appropriate telephone number listed on the inside back cover.

· ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area.

Signs and Symptoms of ANTU Exposure: Acute exposure to ANTU may result in skin irritation, vomiting, difficult breathing, noisy breathing, pulmonary edema or effusion, low body temperature, and seizures. Antithyroid activity and hyperglycemia may be observed after chronic sublethal exposure.

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

General First Aid:

(General first aid procedures)

If material on fire or involved in fire: Extinguish fire using agent suitable for type of surrounding fire (Material itself does not burn or burns with difficulty). Use water in flooding quantities as fog. Use foam, dry chemical, or carbon dioxide. Keep run-off water out of sewers and water sources. /Naphthylthiourea/

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

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Separated from strong oxidants, silver nitrate, food and feedstuffs.

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place.

Ventilate area of spill. For small quantities, sweep onto paper or other suitable material, place in appropriate container and burn in safe place (such as fume hood). Large quantities may be reclaimed ... If not practical, dissolve in flammable solvent ... and atomize in ... combustion chamber ...

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapours, 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. 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.

Avoid inhalation and skin contact. Do not touch spilled material, stay upwind, keep out of low areas, deny entry. (EPA, 1998)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P072, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids.

Incinerate in a furnace equipped with an alkaline scrubber. Recommendable methods: Incineration & landfill. ... (Peer-review conclusions of an IRPTC expert consultation (May 1985))

Waste treatment methods. 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.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

Acute lung injury is an inflammatory syndrome that increases the permeability of the blood-gas barrier, resulting in high morbidity and mortality. Despite intensive research, treatment options remain limited. /This study/ investigated the protective efficacy of tezosentan, a novel, dual endothelin receptor antagonist, in an experimental model of alpha-naphthylthiourea (ANTU)-induced acute lung injury in rats. ANTU was intraperitoneally (i.p.) injected into rats at a dose of 10 mg/kg. Tezosentan was injected 30 minutes before ANTU was subcutaneously (s.c.) injected at doses of 2, 10, or 30 mg/kg, 60 minutes before ANTU was injected at doses of 2, 10, or 30 mg/kg (i.p.), and 90 minutes before ANTU at a dose of 10 mg/kg (i.p.). Four hours later, the lung weight/body weight (LW/BW) ratio and pleural effusion (PE) were measured. When injected 30 minutes before ANTU at doses of 2, 10, or 30 mg/kg (s.c.), tezosentan had no effect on lung pathology. When injected 60 minutes before ANTU at doses of 2, 10, or 30 mg/kg (i.p.) or 90 minutes before ANTU (10 mg/kg, i.p.), tezosentan significantly decreased the PE/BW ratio and had a prophylactic effect on PE formation at all doses. Therefore, tezosentan may attenuate lung injury. Furthermore, its acute and inhibitory effects on fluid accumulation were more effective in the pleural cavity than in the interstitial compartment in this experimental model.

This study was designed to investigate the possible participation of morphine in pulmonary edema induced by alpha-naphthylthiourea (ANTU), which is a well-known noxious chemical agent in the lung. Injection of ANTU (15 mg/kg i.p.) produced pulmonary edema as indicated by an increase in lung weight/body weight ratio and pleural effusion reaching a maximum within 4 hr in rat. Administration of morphine prior to ANTU significantly inhibited to pulmonary edema with a dose-dependent manner. The protective effect of morphine is prevented by peripheral opioid receptor antagonist, naloxone methiodide. ANTU-treated rats were shown positive by inducible nitric oxide synthase immunohistochemical staining. There was no staining in the control group. On the other hand, the degree of staining was markedly reduced in tissue sections by morphine. These results suggest that previous administration of subcutaneous morphine has preventive effect on ANTU-induced pulmonary inflammatory reaction and its effect mediated via peripheral opioid receptors. Application of naloxone with ANTU has no effect on the lung parameters indicating that endogenous opioids do not modulate ANTU-induced damage.

Iodine or iodide given to animals 6 hours prior to ANTU affords significant protection, but neither is effective after exposure.

... Pretreatment of mice with 4-ipomeanol produced tolerance to alpha-naphthylthiourea. ... /Dose not specified/.

For more Interactions (Complete) data for ALPHA-NAPHTHYLTHIOUREA (11 total), please visit the HSDB record page.

LC50; Species: Anas platyrhychos (Mallard duck) 10 day old; dietary 3,400 ppm for 5 days (95% confidence interval: 2378-4362 ppm)

LC50; Species: Colinus virginianus (Northern bobwhite) 10 day old; dietary 8,200 ppm for 5 days (95% confidence interal: 5,563-12,087 ppm)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3600(SRC), determined from a structure estimation method(2), indicates that alpha-naphthylthiourea is expected to have slight mobility in soil(SRC). The pKa of alpha-naphthylthiourea is estimated as 9.47(3), indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of neutral alpha-naphthylthiourea from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.5X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). The ionic form of alpha-naphthylthiourea is not expected to volatilize because ions do not volatilize. alpha-Naphthylthiourea is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2014).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3600(SRC), determined from a structure estimation method(2), indicates that alpha-naphthylthiourea is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 9.47(3) indicates alpha-naphthylthiourea will exist partially in the anion form at pH values of 5 to 9 and, therefore, volatilization of the ionic form from water surfaces is not expected to be an important fate process(SRC). Volatilization of the neutral form from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 8.5X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). The hydrolysis half-life for alpha-naphthylthiourea is 361 days based on a measured hydrolysis rate constant of 2.2X10-8 L/mol sec at pH 7 and 25 °C(6). According to a classification scheme(7), an estimated BCF of 5.7(SRC), from a log Kow of 1.65(8) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2014).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), alpha-naphthylthiourea, which has an estimated vapor pressure of 1.1X10-6 Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase alpha-naphthylthiourea 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 1.6 hours(SRC), calculated from its rate constant of 2.2X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase alpha-naphthylthiourea may be removed from the air by wet and dry deposition(SRC). alpha-Naphthylthiourea contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The substance can be absorbed into the body by inhalation of its aerosol, through the skin and by ingestion.

inhalation, ingestion

IDENTIFICATION AND USE: Alpha-Naphthyl thiourea (ANTU) is a white, crystalline, or gray odorless powder with a bitter taste. It was first used as a rodenticide for the control of adult Norway rats. It was widely used in the 1940s but has subsequently been replaced by other compounds in most countries including the U.S. It is not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: ANTU is well absorbed by skin contact and inhalation. Oral ingestion may result in vomiting, shortness of breath, bluish discoloration of the skin, pulmonary edema or liver injury. Repeat exposures can injure the thyroid and adrenals, producing hypothyroidism. ANIMAL STUDIES: Oral feeding of ANTU to rats at 10 mg/kg body weight increased the blood glucose levels by 100% after 22 hours. Acute exposure also caused elevated plasma activities of aspartate and alanine aminotransferases and increased the activity of the lactate dehydrogenase 5 (LD5) isoenzyme, suggesting that the liver is one of the targets in poisoning in ANTU-treated rats. Toxic symptoms observed in laboratory animals given repeated doses of alpha-naphthyl thiourea include impaired weight gain and deformities of the legs and feet; inhibition of hair growth and defective hair pigmentation; thyroid hyperplasia and hypercholesterolemia; and fatty degeneration of the liver and bile-duct proliferation. Other effects that have been reported are inhibition of pulmonary aniline hydroxylase activity, increased pulmonary aminopyrine demethylase activity and inhibition of Na+/K+ ATPases in erythrocyte membranes and kidney microsomes. Microsomes from rat liver and lung release atomic sulfur from alpha-naphthyl thiourea. Pulmonary toxicity may result, at least in part, from binding of atomic sulfur to tissue macromolecules in susceptable species. ANTU is mutagenic when metabolized by liver microsomal fractions from rats treated with either Aroclor 1254 or phenobarbital. It also transforms hamster embryo cells in an in vitro carcinogenesis bioassay.

Cough. Laboured breathing. Shortness of breath.

MAY BE ABSORBED!

Abdominal pain. Vomiting. Laboured breathing.

After ingestion of large doses: vomiting, dyspnea (breathing difficulty), cyanosis, coarse pulmonary rales; liver damage

Using a structure estimation method based on molecular connectivity indices(1), the Koc of alpha-naphthylthiourea can be estimated to be 3600(SRC). According to a classification scheme(2), this estimated Koc value suggests that alpha-naphthylthiourea is expected to have slight mobility in soil. The pKa of alpha-naphthylthiourea is estimated as 9.47(3), indicating that this compound will exist partially in anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

P072; As stipulated in 40 CFR 261.33, when alpha-naphthylthiourea, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. ANTU is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .

ANTU is metabolized by rat liver and lung microsomes to alpha-naphthylurea (anu) and atomic sulfur. ANTU pulmonary toxicity may result, in part, from covalent binding of sulfur /SRP: or a metabolite containing carbonyl carbon of ANTU to macromolecules of liver and lung microsomes/.

...The covalent binding of atomic sulfur released in the cytochrome P-450 monooxygenase-catalyzed metabolism of thiono-sulfur compounds is responsible for monooxygenase activity being inhibited. Damage to liver and possibly lung edema and neoplasia result from the covalent binding of the electrophilic S-oxides, S-dioxides or carbene derivatives of these S-oxides and S-dioxides to tissue macromolecules.

The in vivo administration of the radiolabeled lung toxin alpha-naphthylthiourea (ANTU) to rats leads to the covalent binding of radioactivity to the macromolecules of the lung and liver. Very little radioactivity is bound in these organs when an equal amount of the (14)C-labeled oxygen analog of ANTU, (14)C-alpha-naphthylurea (ANU), is administered. ANU is essentially nontoxic to rats. ANTU is metabolized in vitro by lung and liver microsomes to an intermediate which covalently binds to the macromolecules of the microsomes. This covalent binding, which requires NADPH, leads to a decrease in mixed-function oxidase activity and to a decrease in the level of cytochrome P-450 detectable as its CO complex. Incubation of microsomes with ANTU in the absence of NADPH or with ANU in the presence of NADPH, has no effect on these parameters. Pretreatment of rats with small nonlethal doses of ANTU daily for 5 days brings about a decrease in the activity of the mixed-function oxidase enzyme system in the lung which metabolizes parathion. In addition, this pretreatment decreases the toxicity of ANTU and leads to a decrease in the amount of radioactivity bound to the macromolecules of the lung when the animals are given a lethal dose of (35)S-ANTU.

The in vitro metabolism of the lung toxin alpha-naphthylthiourea (ANTU) was examined using [(35)S] and [(14)C] ANTU and microsomes isolated from the liver and lung of phenobarbital-treated rats. ANTU was metabolized by this system to alpha-naphthylurea (ANU). A portion of the sulfur released in this reaction binds covalently to microsomal proteins. The Km values for the formation of ANU using the liver and lung microsomal system were 4.56 and 4.18 mM, respectively. The metabolism of ANTU to ANU required NADPH for optimum activity and was inhibited by carbon monoxide and anerobic conditions. The reaction was also inhibited in the presence of an antibody to rat liver cytochrome P450. A portion of the sulfur released during the oxidative desulfuration of [(35)S] ANTU to ANU was shown to react with the sulfhydryl group of cysteine residues in the microsomal proteins to form a hydrodisulfide.

... Workers handling thiourea products showed ready penetration through skin leading to destructive changes in the thyroid gland.

.../Detected in tissues only if material has/ been obtained within 24 hr of ingestion of a fairly large quantity of ANTU. The results of chemical examination of tissues for ANTU are uniformly negative in cases where the animals have survived for more than 24 hours.

Twenty hr after oral admin of 10 mg/kg of ANTU to albino rats, 40% was excreted in urine and less than 1% in feces. Approx 36% of urinary ANTU was excreted in the original form, and the rest in 3 metabolites.

Max ANTU content reached in rat pleural effusion, lung, skeletal muscles, and pancreas 4 hr after oral administration of 10 mg/kg. Albumin contained 80% of ANTU present in serum and pleural effusion.

Absorption of 1-naphthylthiourea from the gut is rapid, especially in the presence of fat. Differences between oral and parenteral LD50 values suggest that gut absorption of this compound may be incomplete in some species.

No ANTU products are registered in the USA. [LaDou, 4th Ed., p. 564]

Farming (Pesticides) [Category: Industry]

For alpha-naphthylthiourea (USEPA/OPP Pesticide Code: 004501) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Laboratory reagent and chemical intermediate

Rodenticide. Specific control for the adult Norway rat (Rattus norvegicus); less toxic to other Rattus species. /Former US/

Rodenticide /Former US/

(1977) No Data

(1982) No Data

(1972) 3.753X10+6 g

(1975) 9.01X10+5 g (last report of imports through USA principal customs districts)

(1977) No Data

(1982) No Data

(1947) 6.4X10+7 g

Production has not been reported since 1953.

(1977) No Data

(1982) NOT PRODUCED COMMERCIALLY IN USA

Prepared from alpha-naphthylamine and ammonium or potassium or sodium thiocyanate; ... from alpha-naphthylisothiocyanate by treatment with alcoholic ammonia.

From alpha-naphthylthiocarbamide and alkali or ammonium thiocyanate.

... Prepared by heating a mixture of 1-naphthylamine hydrochloride, NH4SCN, and a large amount of water for 14-16 hr while keeping its volume constant by adding an additional amount of water, to give a 97% yield.

Thiourea, N-1-naphthalenyl-: ACTIVE

The WHO Recommended Classification of Pesticides by Hazard identifies ANTU as an active ingredient believed to be obsolete or discontinued for use as a pesticide.

... Developed as an outgrowth of the observation that phenylthiourea kills rats but is not toxic to man. Many derivatives were prepared before one was found which had the same high toxicity to rodents without the bitter taste of phenylthiourea. ANTU proved to be the most effective.

1-Naphthylthiourea was first produced commercially in the US in 1946 (US Tariff Commission, 1948)...

1-Naphthylthiourea is believed to be produced by one company each in France & the Federal Republic of Germany. It is not produced commercially in Japan.

For more General Manufacturing Information (Complete) data for ALPHA-NAPHTHYLTHIOUREA (6 total), please visit the HSDB record page.