α-Naphthylthiourea

202.28

202.28

778118

201-706-3

UKY0H6XJ4J

0973

3287

1651

DTXSID8020919

Prisms from alcohol|Colorless ... solid|White, crystalline or gray powder

2930909059

70.1

1.66 (calculated)

Grayish to beige-brown Crystals or Crystalline Powder

1 g/cm³

198 °C

Decomposes

May burn but will not ignite readily (EPA, 1998)

1.794

600 mg/L at 20 °C (quoted, Windholz et al., 1983)

Poison room

Low

6.99

Oral-rat LD50: 6 mg/kg; Oral-Mouse LD50: 5 mg/kg

Thermal decomposition of toxic nitrogen oxide and sulfur oxide gases

Odorless

Bitter taste

Henry's Law constant = 8.51X10-9 atm-cu m/mol at 25 °C (est)

pKa = 9.47 (est)

Noncombustible solid; decomposes|Usually grey powder /commercial preparation/|Blue-grey powder /Technical grade/|Stable on exposure to air and to sunlight|Hydroxyl radical reaction rate constant = 2.21 X10-10 cu cm/molec-sec at 25 °C (est)

Slightly soluble in water.

Amides and Imides

ANTU is incompatible with the following: Strong oxidizers, silver nitrate (NIOSH, 2016).

Noncombustible Solid

I

6.1

1651

2

28-40

28-36/37-45-25-23

YT9275000

T+

The warehouse is ventilated, low temperature and dry; stored and transported separately from food materials

Stable under recommended storage conditions.

P301 + P310 + P330

H300-H351

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.

Incompatibilities: Contact with strong oxidizers may cause fires and explosions.|Strong oxidizers, silver nitrate.|Incompatible materials: Strong oxidizing agents.

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.

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

|Danger|H300: Fatal if swallowed [Danger Acute toxicity, oral]|P201, P202, P264, P270, P281, P301+P310, P308+P313, P321, P330, P405, and P501|H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]|Aggregated GHS information provided by 44 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|P260, P264, P270, P301+P310, P307+P311, P321, P330, P405, and P501

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

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

Skin: No recommendation is made specifying the need for personal protective equipment for the body. Eyes: No recommendation is made specifying the need for eye protection. Wash skin: No recommendation is made specifying the need for washing the substance from the skin (either immediately or at the end of the work shift). Remove: No recommendation is made specifying the need for removing clothing that becomes wet or contaminated. Change: Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premise. (NIOSH, 2016)|Respirator Recommendations: Up to 3 mg/cu m:[Table#3201]|Respirator Recommendations: Up to 7.5 mg/cu m:[Table#3202]|Respirator Recommendations: Up to 15 mg/cu m:[Table#3203]|Respirator Recommendations: Up to 100 mg/cu m:[Table#3204]|For more Personal Protective Equipment (PPE) (Complete) data for ALPHA-NAPHTHYLTHIOUREA (11 total), please visit the HSDB record page.|(See protection codes)

/To fight fire use:/Powder, water spray, foam, carbon dioxide.

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.

Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), sulphur oxides.

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.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|SRP: Contaminated protective clothing should be segregated in a manner such that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.|Do not eat or smoke in area where ANTU is being handled, processed, or stored.|Individuals who handle ANTU should wash their hands thoroughly with soap and water before smoking or eating.|For more Preventive Measures (Complete) data for ALPHA-NAPHTHYLTHIOUREA (16 total), please visit the HSDB record page.

/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Health: TOXIC; inhalation, ingestion, or skin contact with material may cause severe injury or death. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Effects of contact or inhalation may be delayed. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. /Naphthylthiourea/|/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Fire or Explosion: 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. 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. /Naphthylthiourea/|/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Public Safety: CALL Emergency Response Telephone Number ... As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate enclosed areas. /Naphthylthiourea/|/GUIDE 153: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. /Naphthylthiourea/|For more DOT Emergency Guidelines (Complete) data for ALPHA-NAPHTHYLTHIOUREA (8 total), please visit the HSDB record page.

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./|The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.|The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.

... Dermal contact can cause skin and mucous membrane irritation.

Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 0.3 mg/cu m.

Recommended Exposure Limit: 10-hour Time-Weighted Average: 0.3 mg/cu m.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Carefully collect remainder. Then store and dispose of according to local regulations.

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

Evaporation at 20 °C is negligible; a harmful concentration of airborne particles can, however, be reached quickly.

Exposure could cause lung oedema. Medical observation is indicated.

PREVENT DISPERSION OF DUST! STRICT HYGIENE! IN ALL CASES CONSULT A DOCTOR!

Use local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear safety goggles, face shield or eye protection in combination with breathing protection.

P072; An acute hazardous waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate.

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 ... .

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)).

most toxic

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.

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.

LD50 Rat (Norway wild, adult) ip 6.20-8.10 mg/kg|LD50 Chicken ig 4250 mg/kg|LD50 Chicken ip 2500 mg/kg|LD50 Rabbit ip or ig >400 mg/kg|For more Non-Human Toxicity Values (Complete) data for ALPHA-NAPHTHYLTHIOUREA (13 total), please visit the HSDB record page.

Individuals with liver or respiratory tract diseases.

alpha-Naphthylthiourea is not known to occur as a natural product.

alpha-Naphthylthiourea's production and use as a laboratory reagent and chemical intermediate(1) may result in its release to the environment through various waste streams(SRC). Its former use in the US as a rodenticide(2) resulted in its direct release to the environment(SRC).

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 rate constant for the vapor-phase reaction of with photochemically-produced hydroxyl radicals has been estimated as 2.2X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 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(2). alpha-Naphthylthiourea contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 5.7 was calculated in fish for alpha-naphthylthiourea(SRC), using a log Kow of 1.65(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

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).

The Henry's Law constant for alpha-naphthylthiourea is estimated as 8.5X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that neutral alpha-naphthylthiourea is expected to be essentially nonvolatile from moist soil and water surfaces(2). 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). alpha-Naphthylthiourea is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-6 mm Hg(SRC), determined from a fragment constant method(1).

alpha-Naphthylthiourea was not detected (detection limit not reported) in wheat, barley or oat grain samples from Ciudad Real, Spain(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 1450 workers were potentially exposed to alpha-naphthylthiourea in the US(1). The NOES Survey does not include farm workers. Occupational exposure to alpha-naphthylthiourea may occur through inhalation and dermal contact with this compound at workplaces where alpha-naphthylthiourea is produced or used. General population exposure should be low or non-existent since alpha-naphthylthiourea is no longer used in the US(SRC).

Substances used to destroy or inhibit the action of rats, mice, or other rodents. (See all compounds classified as Rodenticides.)

... 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.

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.

Suggestions that the presence of an impurity in ANTU, beta-naphthylamine, may increase risk of bladder cancer, remain unsubstantionated.

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)

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. Emergency Life-Support Procedures: Acute exposure to ANTU may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination. Inhalation Exposure: 1. Move victims to fresh air. Emergency personnel should avoid self-exposure to ANTU. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 4. Transport to a health care facility. Dermal/Eye Exposure: 1. Remove victims from exposure. Emergency personnel should avoid self-exposure to ANTU. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3. Remove contaminated clothing as soon as possible. 4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes. 5. Wash exposed skin areas thoroughly with water. 6. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 7. Transport to a health care facility. Ingestion Exposure: 1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 3. Vomiting may be induced with syrup of Ipecac. If elapsed time since ingestion of ANTU is unknown or suspected to be greater than 30 minutes, do not induce vomiting and proceed to Step 4. Ipecac should not be administered to children under 6 months of age.Warning: Syrup of Ipecac should be administered only if victims are alert, have an active gag-reflex, and show no signs of impending seizure or coma. If ANY uncertainty exists, proceed to Step 4.The following dosages of Ipecac are recommended: children up to 1 year old, 10 mL (1/3 oz); children 1 to 12 years old, 15 mL (1/2 oz); adults, 30 mL (1 oz). Ambulate (walk) the victims and give large quantities of water. If vomiting has not occurred after 15 minutes, Ipecac may be readministered. Continue to ambulate and give water to the victims. If vomiting has not occurred within 15 minutes after second administration of Ipecac, administer activated charcoal. 4. Activated charcoal may be administered if victims are conscious and alert. Use 15 to 30 g (1/2 to 1 oz) for children, 50 to 100 g (1-3/4 to 3-1/2 oz) for adults, with 125 to 250 mL (1/2 to 1 cup) of water. 5. Promote excretion by administering a saline cathartic or sorbitol to conscious and alert victims. Children require 15 to 30 g (1/2 to 1 oz) of cathartic; 50 to 100 g (1-3/4 to 3-1/2 oz) is recommended for adults. 6. Transport to a health care facility. (EPA, 1998)|(See procedures)

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.

Treatment includes gastrointestinal decontamination with activated charcoal, supportive care, and monitoring of electrolytes and glucose. Pulmonary edema may be delayed up to 72 hours. Patients ingesting more than 5 mg/kg body weight should be admitted for observation.|Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Naphthalene and Related Compounds/|Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Naphthalene and Related Compounds/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Start IV administration of 0.9% saline (NS) or lactated Ringer's (LR). Adequate hydration must be maintained to prevent renal failure secondary to myoglobinuria unless signs of cerebral or pulmonary edema are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Naphthalene and related compounds/

/SIGNS AND SYMPTOMS/ /Oral ingestion/ may cause vomiting, shortness of breath, and bluish discoloration of the skin.|/SIGNS AND SYMPTOMS/ There are no reports of human poisonings with ANTU. However, several cases involving a combination of chloralose and ANTU were reported in France; symptoms included motor agitation and coma, both caracteristic of chloralose poisonings, and pulmonary effects, due to ANTU, but all patients recovered. Suggestions that the presence of an impurity in ANTU, beta-naphthylamine, may increase risk of bladder cancer, remain unsubstantionated.|/SIGNS AND SYMPTOMS/ Large overdoses present with lassitude, anorexia, abdominal pain, hypoxia, cyanosis, dyspnea, and rales. Motor and sensory peripheral neuropathy, autonomic dysfunction, and CNS disorders have /all/ been reported. Acute inhalation of dust produces coughing, dyspnea, pulmonary edema, tracheitis and pneumonitis. Dermal contact can cause skin and mucous membrane irritation.|/CASE REPORTS/ The rodenticide ANTU (alpha-naphthylthiourea) was used in the United Kingdom mainly in the late 1940's and early 1950's. The product then contained up to 0.2% of beta-naphthylamine as an impurity, and it was finally withdrawn in 1967 as a suspected carcinogen. Fourteen cases of urothelial tumors among rodent /exterminators/ exposed to ANTU are reported: in one district 4/27 staff were affected, and in another area 2/10. ...|For more Human Toxicity Excerpts (Complete) data for ALPHA-NAPHTHYLTHIOUREA (8 total), please visit the HSDB record page.

1-naphthylthiourea

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

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

Cough. Laboured breathing. Shortness of breath.

MAY BE ABSORBED!

respiratory system, blood, liver

1-Naphthylthiourea is available as 10% active baits in suitable protein- or carbohydrate-rich materials & as a 20% tracking powder.

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.

Product analysis is by reaction with silver nitrate & titration of liberated nitric acid|Residues may be determined by addn of bromine to an acetic acid soln, & violet color produced in alkali measured colorimetrically|Method: NIOSH S276; Procedure: HPLC; Analyte: ANTU; Matrix: air; Estimated Detection Level: 5 ug/sample.

A polarographic thin-layer detector for high performance liquid chromatography was devised ... and applied to ... detection with reactivation of the electrode surface by voltage pulses and ... is suitable for detection of cmpd that form insoluble or complex Hg salts, eg, thiourea. Thiourea and its derivatives can be separated and determined in a wide concn range and the detection limit for thiourea corresponds to 2 ng injected. It can be detected directly in urine.