hexamethylenetetramine

H228: Flammable solid [Danger Flammable solids]

H317: May cause an allergic skin reaction [Warning Sensitization, Skin]

P210, P240, P241, P261, P272, P280, P302+P352, P321, P333+P317, P362+P364, P370+P378, and P501 (click each P-code to see the statement)

H228 (100%): Flammable solid [Danger Flammable solids]

H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]

Aggregated GHS information provided per 1051 reports by companies from 19 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

H314 (100%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

H334 (100%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]

H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]

P203, P233, P260, P261, P264, P270, P271, P272, P280, P284, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P318, P321, P330, P333+P317, P342+P316, P362+P364, P363, P403, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

H361: Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]

P203, P210, P240, P241, P260, P261, P264, P270, P272, P280, P302+P352, P318, P319, P321, P333+P317, P362+P364, P370+P378, P405, and P501 (click each P-code to see the statement)

H316: Causes mild skin irritation [Warning Skin corrosion/irritation]

H320: Causes eye irritation [Warning Serious eye damage/eye irritation]

H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]

P203, P210, P233, P240, P241, P260, P261, P264, P264+P265, P270, P271, P272, P280, P284, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P333+P317, P337+P317, P342+P316, P362+P364, P370+P378, P403, P405, and P501 (click each P-code to see the statement)

P210, P233, P240, P241, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P370+P378, P403, and P501 (click each P-code to see the statement)

Fresh air, rest. Refer for medical attention.

Remove contaminated clothes. Rinse and then wash skin with water and soap. Refer for medical attention .

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

Rinse mouth. Give a slurry of activated charcoal in water to drink. Refer for medical attention .

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

General First Aid:

· Call 911 or emergency medical service.

· Ensure that medical personnel are aware of the material(s) involved, take precautions to protect themselves and avoid contamination.

· Move victim to fresh air if it can be done safely.

· Administer oxygen if breathing is difficult.

· If victim is not breathing:

-- DO NOT perform mouth-to-mouth resuscitation; the victim may have ingested or inhaled the substance.

-- If equipped and pulse detected, wash face and mouth, then give artificial respiration using a proper respiratory medical device (bag-valve mask, pocket mask equipped with a one-way valve or other device).

-- If no pulse detected or no respiratory medical device available, provide continuous compressions. Conduct a pulse check every two minutes or monitor for any signs of spontaneous respirations.

· Remove and isolate contaminated clothing and shoes.

· For minor skin contact, avoid spreading material on unaffected skin.

· In case of contact with substance, remove immediately by flushing skin or eyes with running water for at least 20 minutes.

· For severe burns, immediate medical attention is required.

· Effects of exposure (inhalation, ingestion, or skin contact) to substance may be delayed.

· Keep victim calm and warm.

· Keep victim under observation.

· For further assistance, contact your local Poison Control Center.

· Note: Basic Life Support (BLS) and Advanced Life Support (ALS) should be done by trained professionals.

Specific First Aid:

· Removal of solidified molten material from skin requires medical assistance.

In Canada, an Emergency Response Assistance Plan (ERAP) may be required for this product. Please consult the shipping paper and/or the "ERAP" section.

Excerpt from ERG Guide 133 [Flammable Solids]:

SMALL FIRE: Dry chemical, CO2, sand, earth, water spray or regular foam.

LARGE FIRE: Water spray, fog or regular foam. If it can be done safely, move undamaged containers away from the area around the fire.

FIRE INVOLVING METAL PIGMENTS OR PASTES (E.G. "ALUMINUM PASTE"): Aluminum Paste fires should be treated as a combustible metal fire. Use DRY sand, graphite powder, dry sodium chloride-based extinguishers or class D extinguishers. Also, see ERG Guide 170.

FIRE INVOLVING TANKS, RAIL TANK CARS OR HIGHWAY TANKS: Cool containers with flooding quantities of water until well after fire is out. For massive fire, use unmanned master stream devices or monitor nozzles; if this is impossible, withdraw from area and let fire burn. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks in direct contact with flames. (ERG, 2024)

Use water spray, foam, powder.

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

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Use water spray to cool unopened containers.

Solid streams of water may spread fire. Use water in flooding quantities as fog. Use dry chemical, graphite, or dry earth.

· 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.

· Keep unauthorized personnel away.

· Stay upwind, uphill and/or upstream.

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

· Do not touch or walk through spilled material.

Small Dry Spill

· With clean shovel, place material into clean, dry container and cover loosely; move containers from spill area.

Large Spill

· Wet down with water and dike for later disposal.

· Prevent entry into waterways, sewers, basements or confined areas.

Excerpt from ERG Guide 133 [Flammable Solids]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area for at least 25 meters (75 feet) in all directions.

LARGE SPILL: Consider initial downwind evacuation for at least 100 meters (330 feet).

FIRE: If tank, rail tank car or highway tank 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, 2024)

Immediate precautionary measure

· Isolate spill or leak area for at least 25 meters (75 feet) in all directions.

· Consider initial downwind evacuation for at least 100 meters (330 feet).

· If tank, rail tank car or highway tank 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.

Personal protection: filter respirator for organic gases and particulates adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting. Wash away remainder with plenty of water.

Accidental Release Measures: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Remove all sources of ignition. 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: Sweep up and shovel. Contain spillage, and then collect with an electrically protected vacuum cleaner or by wetbrushing and place in container for disposal according to local regulations. Keep in suitable, closed containers for disposal.

Toxic compd can be removed by reverse osmosis. Hexamethyleneamine treated with oxygen in presence of pyrolusite ores to form HCO2H & NaNO3 which can be removed by biol treatment.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Product: Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting as this material is highly flammable. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed. Keep away from sources of ignition - No smoking. Take measures to prevent the build up of electrostatic charge.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits 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.

For more Preventive Measures (Complete) data for METHENAMINE (8 total), please visit the HSDB record page.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should store this chemical under refrigerated temperatures, and keep it away from oxidizing materials. Protect from exposure to moisture. (NTP, 1992)

Separated from strong acids and strong oxidants. Dry.

Keep container tightly closed in a dry and well-ventilated place. Hygroscopic. Storage class (TRGS 510): Flammable solid hazardous materials

· Wear positive pressure self-contained breathing apparatus (SCBA).

· Structural firefighters' protective clothing provides thermal protection but only limited chemical protection.

28 [ppm]

310 [ppm]

1800 [ppm]

1.0 [mg/m3], inhalable fraction and vapor

(inhalable fraction and vapour): 1 mg/m

sensitization of skin (SH)

Small Fire

· Dry chemical, CO2, sand, earth, water spray or regular foam.

Large Fire

· Water spray, fog or regular foam.

· If it can be done safely, move undamaged containers away from the area around the fire.

Fire Involving Metal Pigments or Pastes (e.g. "Aluminum Paste")

· Aluminum Paste fires should be treated as a combustible metal fire. Use DRY sand, graphite powder, dry sodium chloride-based extinguishers or class D extinguishers. Also, see GUIDE 170.

Fire Involving Tanks, Rail Tank Cars or Highway Tanks

· Cool containers with flooding quantities of water until well after fire is out.

· For massive fire, use unmanned master stream devices or monitor nozzles; if this is impossible, withdraw from area and let fire burn.

· Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank.

· ALWAYS stay away from tanks in direct contact with flames.

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

The substance is mildly irritating to the eyes and skin.

Repeated or prolonged contact may cause skin sensitization. Repeated or prolonged inhalation may cause asthma.

Residues of hexamethylenetetramine are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops or to raw agricultural commodities after harvest. Use: Preservative. Limit: For use in citrus washing solutions only at not more than 1%.

Residues of hexamethylenetetramine are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Stabilizer for carriers in solid pesticide formulations. Limit: None.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. Flame retardant antistatic protective clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

For more Personal Protective Equipment (PPE) (Complete) data for METHENAMINE (6 total), please visit the HSDB record page.

NO open flames. Closed system, dust explosion-proof electrical equipment and lighting. Prevent deposition of dust.

PREVENT DISPERSION OF DUST!

Use local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear face shield or eye protection in combination with breathing protection.

Do not eat, drink, or smoke during work.

Hexamethylenetetramine appears as odorless white crystalline powder or colorless lustrous crystals. Sublimes in a vacuum at about 505 °F with some decomposition. Solutions are strong bases (pH of 0.2 molar aqueous solution is 8.4). (NTP, 1992)

Liquid; Dry Powder; Liquid; Dry Powder; Large Crystals

Colourless or white crystalline powder

White, crystalline powder or colorless, lustrous crystals; [HSDB]

HYGROSCOPIC COLOURLESS CRYSTALS OR WHITE CRYSTALLINE POWDER.

Crystallizes from ethanol as colorless, hygroscopic rhombododecahedra.

Colorless crystalline solid

Colorless, lustrous crystals or white crystalline powder

White, crystalline powder or colorless, lustrous crystals

Odorless

Practically odorless

Sublimes (NTP, 1992)

536 °F (sublimes) (NTP, 1992)

Sublimes at about 260 °C without melting and with partial decomposition

Sour taste; mp: 127-130 °C; ph of soln 4 /Methenamine mandelate/

Odorless, crystalline powder; melting point: ~190 °C with decomposition; soluble in 8 parts water; slight soluble in alcohol /Methenamine sulfosalicylate/

> 250 °C

482 °F (NTP, 1992)

250 °C (482 °F) - closed cup

250 °C c.c.

greater than or equal to 100 mg/mL at 68 °F (NTP, 1992)

In water, 302,300 mg/L at 25 °C

Solubility of methenamine in 100 g of various solvents at 20 °C is: 13.4 g chloroform, 7.25 g in methanol, 2.89 g in absolute ethanol, 0.65 g in acetone, 0.23 g in benzene, 0.14 g in xylene, 0.06 g in ether, and near zero in petroleum ether.

At 12 °C, 81.3 g dissolves in 100 g of water; the solubility decreases slightly with increasing temperature.

Freely soluble in water; practically insoluble in petroleum ether

For more Solubility (Complete) data for METHENAMINE (6 total), please visit the HSDB record page.

449 mg/mL at 12 °C

Solubility in water: good

>21 [ug/mL] (The mean of the results at pH 7.4)

1.35 at 68 °F (USCG, 1999) - Denser than water; will sink

1.3394 g/cu cm at 22 °C

Density: 1.27 at 25 °C

1.33 g/cm³

1.331 @ -5°C

4.9 (NTP, 1992) - Heavier than air; will sink (Relative to Air)

4.9 (Air = 1)

Relative vapor density (air = 1): 4.9

0.004 [mmHg]

6.1X10-4 mm Hg at 25 °C

log Kow = -2.18 at pH 7-9, 20 °C

Highly flammable. Burns readily on contact with a flame with a smokeless flame. Finely powdered dust is significant dust explosion hazard. Water soluble.

Amines, Phosphines, and Pyridines

Highly Flammable

HEXAMETHYLENETETRAMINE is hygroscopic. It is sensitive to exposure to heat. This chemical is incompatible with oxidizing agents. It is also incompatible with acids. It reacts violently with sodium peroxide. It reacts explosively with 1-bromopentaborane(9) at temperatures above 194 °F. The complex with iodine deflagrates at 280 °F. The 1:1 addition complex with iodoform has exploded at 352 °F. It is corrosive to some metals, such as aluminum and zinc (NTP, 1992). Special Hazards of Combustion Products: Formaldehyde gas and ammonia may be given off when hot (USCG, 1999).

Incompatible materials: Strong acids, acids, strong oxidizing agents

Can react with oxidizing materials. Explosive reaction with acetic acid + acetic anhydride + ammonium nitrate + nitric acid; 1-bromopenta borane(9) (above 90 °C); iodoform (at 178 °C); iodine (at 138 °C). Reaction with nitric acid + acetic anhydride forms the military explosives RDX and HMX. Reacts violently with Na2O2.

On the basis of the animal and clinical data presented in this report, the CIR Expert Panel concludes that Methenamine is safe for cosmetic use at concentrations not to exceed 0.16% in formulation. It cannot be concluded that Methenamine is safe for use in cosmetic products intended to be aerosolized.

Safe for use in cosmetics, with qualifications

IDENTIFICATION AND USE: Methenamine is a white or colorless crystalline solid. It is an anti-infective agent. Methenamine hippurate tablets, USP are indicated for prophylactic or suppressive treatment of frequently recurring urinary tract infections when long-term therapy is considered necessary. Non-medical uses include the following: in adhesives, coatings, and sealing compounds; as cross-linking agent for hardening phenol-formaldehyde resin and vulcanizing rubber; as corrosion inhibitor for steel; as fuel tablets for camping stoves; as stabilizer for lubricating and insulating oils; in the chemical detection of metals; in the preservation of hides; as dye fixative; for the manufacture of explosive compounds; antimicrobial food additive. HUMAN EXPOSURE AND TOXICITY: GI distress frequently is caused by doses >500 mg four times a day, even with enteric coated tablets. Painful and frequent micturition, albuminuria, hematuria, and rashes may result from doses of 4 to 8 g/day given for longer than 3-4 weeks. Inhalation may cause asthma-like reactions in previously sensitized individuals. Vapors or solutions have produced skin irritation. Methenamine does not appear to be linked to congenital defects. ANIMAL STUDIES: Studies on rats, mice, cats, and guinea pigs suggest that methenamine is moderately toxic following acute exposure. Mild irritation occurred when a 5% solution of a mixture that contained 40% methenamine was placed on the skin of guinea pigs. In chronic toxicity studies in dogs and rats receiving oral methenamine, gastric and bladder irritation occurred with some hemorrhagic sites and ulceration. Methenamine hippurate has been administered to rats for 12 months and to monkeys for 6 months at dosages equivalent to twice the usual recommended human dosage without evidence of adverse effects. Dogs have received single IV dosages of up to 600 mg/kg of methenamine hippurate without overt toxic effects.

Hexamethylenetetramine

Pharmaceutical

Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

In prospective controlled trials, methenamine was generally well tolerated at conventional doses and no episodes of serum aminotransferase elevations or clinically apparent liver injury were reported. Since its approval and in over 100 years of general use, there have been no reports of clinically apparent liver injury attributable to methenamine. Thus, clinically apparent liver injury from methenamine must be rare if it occurs at all.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

No indication of carcinogenicity to humans (not listed by IARC).

◉ Summary of Use during Lactation

Both the hippurate and mandelate salts of methenamine pass into milk in small quantities and appear acceptable to use, even while nursing a newborn.

◉ Effects in Breastfed Infants

Four newborn infants were allowed to breastfeed in one study after a maternal dose of 1 gram of methenamine hippurate. No adverse effects were reported.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

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

Redness. Pain.

Abdominal pain. Nausea. Vomiting.

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

ACGIH Carcinogen - Not Classifiable.

LD50 Rat intravenous 9200 mg/kg

LD50 Mouse subcutaneous 215 mg/kg

/In vet use/...in vivo synergism with antimicrobials has been demonstrated.

Diuretics, such as...thiazides can alkalinize urine & thus theoretically would limit usefulness of methenamine as well as its mandelate & hippurate salts...

Formaldehyde and some sulfonamides (e.g., sulfamethizole, sulfathiazole (not commercially available in the US)) form an insoluble precipitate in acid urine; therefore, methenamine salts should not be administered concomitantly with sulfonamides.

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 if 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. /Aldehydes 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. Aggressive airway management may be necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Anticipate seizures and treat if necessary ... . Monitor for shock and treat if necessary ... . Monitor for pulmonary edema 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 ... . /Aldehydes and Related Compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Intubation should be considered at the first sign of upper airway obstruction caused by edema. Positive-pressure ventilation techniques with a bag-valve-mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Start IV administration of D5W TKO. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aldehydes and Related Compounds/

VET: Large oral overdosages should be handled using established gut emptying protocols, maintaining hydration status and supporting as required.

/SIGNS AND SYMPTOMS/ GI distress frequently is caused by doses >500 mg four times a day, even with enteric coated tablets. Painful and frequent micturition, albuminuria, hematuria, and rashes may result from doses of 4 to 8 g/day given for longer than 3-4 weeks.

/SIGNS AND SYMPTOMS/ ... is a skin sensitizer, and vapors or solutions have produced skin irritation.

/SIGNS AND SYMPTOMS/ Inhalation may cause asthma-like reactions in previously sensitized individuals.

/CASE REPORTS/ A 59-year-old woman presented with acute onset headache. She had a long history of recurrent urinary tract infections. Urological investigations had revealed bladder diverticula and a sacral nerve bladder stimulator had been implanted (to promote bladder emptying). However, despite this, she continued to have urinary tract infections and she was started on long-term prophylactic antibiotics. She had previously taken ciprofloxacin and nitrofurantoin, but 3 days prior to her neurological symptoms, she had started methenamine. On the day that she presented, she developed lower abdominal pain, quickly followed by a rapidly worsening generalised headache with vomiting. A CT head showed a right-sided SAH, with blood in the Sylvian fissure. A cerebral digital subtraction angiogram (DSA) revealed irregularity of several cerebral arteries (a posterior branch of the right middle cerebral artery and both superior cerebellar arteries) but no aneurysm or arteriovenous malformation. A lumbar puncture confirmed subarachnoid blood and blood tests for causes of systemic vasculitis were negative. A diagnosis of RCVS was made and methenamine was stopped. Her headache slowly improved over the next few days and she was discharged. A follow-up DSA at 3 months was within normal limits and on follow-up, 8 months after presentation, she has had no further neurological events.

For more Human Toxicity Excerpts (Complete) data for METHENAMINE (7 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ The dose at which mice begin to die following acute oral exposure is reported to be 512 mg/kg. Injection (intravenous, intraperitoneal, subcutaneous) LD50's in rats, mice, cats, and guinea pigs range from 200 to 512 mg/kg. This limited information suggests that /methenamine/ is moderately toxic following acute exposure.

/LABORATORY ANIMALS: Acute Exposure/ No skin irritation was seen from a neoprene sponge containing an unspecified concentration of HMTA, and mild irritation occurred when a 5% solution of a mixture that contained 40% HMTA was placed on the skin of guinea pigs.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In chronic toxicity studies in dogs and rats receiving oral methenamine in a dosage of 50-200 mg/kg daily and 0.8-6.4 g/kg daily, respectively, gastric and bladder irritation occurred with some hemorrhagic sites and ulceration. Methenamine hippurate has been administered to rats for 12 months and to monkeys for 6 months at dosages equivalent to twice the usual recommended human dosage without evidence of adverse effects.

/VETERINARY CASE REPORTS/ Dogs have received single IV dosages of up to 600 mg/kg of methenamine hippurate without overt toxic effects.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of December 17, 2015: http://actor.epa.gov/dashboard/]

Methenamine hippurate and methenamine mandelate are contraindicated in patients with renal insufficiency; methenamine hippurate also is contraindicated in patients with severe hepatic insufficiency or severe dehydration.

LC50; Species: Nitocra spinipes (Harpacticoid Copepod) adult, length 0.6-0.8 mm; Conditions: saltwater, static, 10 °C, pH 7.8, salinity 7 ppt, alkalinity 75 mg/L CaCO3, dissolved oxygen >5 mg/L; Concentration: 92500000 ug/L for 96 hr (95% confidence interval: 26800000-305000000 ug/L) /formulation/

LC50; Species: Alburnus alburnus (Bleak) length 8 cm; Conditions: saltwater, static, 10 °C, pH 7.8, salinity 7 ppt, alkalinity 75 mg/L CaCO3, dissolved oxygen >5 mg/L; Concentration: >10000000 ug/L for 96 hr /formulation/

LC50; Species: Pimephales promelas (Fathead Minnow) 33 days, length 18.8 mm, weight 0.096 g; Conditions: freshwater, flow through, 25.2 °C, pH 7.8, hardness 44.9 mg/L CaCO3, dissolved oxygen 5.8 mg/L; Concentration: 49800000 ug/L for 96 hr (95% confidence interval: 44600000-55600000 ug/L) /99% purity/

LC50; Species: Cyprinodon variegatus (Sheepshead Minnow); Conditions: saltwater, static, pH 7.7, salinity 20.5 ppt, alkalinity 174 mg/L CaCO3; Concentration: 49000000 ug/L for 96 hr (95% confidence interval: 35885000-66908000 ug/L) /formulation/

Methenamine's production and use as an ammonia or formaldehyde donor in the production of resins, vulcanization agents and in fuel tablets for camping stoves, as well as its administration as a medication may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 6.1X10-4 mm Hg at 25 °C indicates methenamine will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase methenamine will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 45 minutes. Particulate-phase methenamine will be removed from the atmosphere by wet and dry deposition. If released to soil, methenamine is expected to have very high mobility based upon an estimated Koc of 10. The pKa of methenamine is 4.89, indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 3.7X10-10 atm-cu m/mole. Methenamine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Various biolodegradation screening studies have observed between 28-100% degradation of methenamine suggesting that biodegradation is an important environmental fate process in soil and water. However, part (or most) of the degradation may be explained by hydrolysis to form formaldehyde and ammonia followed by biodegradation with the degradation rate increasing with acidity. If released into water, methenamine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is expected to be an important fate process in water, especially in acidic waters. Aqueous hydrolysis half-lives of 13.8 hours and 1.6 hours have been measured at 37.5 °C and pH 5.8 and pH 2 respectively. Occupational exposure to methenamine may occur through inhalation and dermal contact with this compound at workplaces where methenamine is produced or used. Monitoring and use data indicate that the general population may be exposed to methenamine via inhalation and dermal contact with consumer products containing methenamine. The general public exposure to methenamine may also be by direct medical treatment. (SRC)

Methenamine's production and use as an ammonia or formaldehyde donor in the production of resins, vulcanization agents and in fuel tablets for camping stoves(1,2) as well as its administration as a medication(4) may result in its release to the environment through various waste streams(SRC). Methenamine was identified as a volatile organic compound emitted from various types of furniture coatings that might contribute to indoor air pollution(3).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that methenamine is expected to have very high mobility in soil(SRC). The pKa of methenamine is 4.89(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of methenamine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.7X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 6.1X10-4 mm Hg(5), and water solubility, 3.02X10+5 mg/L(6). Methenamine is not expected to volatilize from dry soil surfaces based on its vapor pressure(SRC). Various biolodegradation screening studies have observed between 28-100% degradation of methenamine(7) suggesting that biodegradation is an important environmental fate process in soil(SRC). However, part (or most) of the degradation may be explained by hydrolysis to form formaldehyde and ammonia followed by biodegradation with the degradation rate increasing with acidity(7). Hydrolysis is expected to be an important fate process, especially in moist acidic soils. Aqueous hydrolysis half-lives of 13.8 hours and 1.6 hours have been measured at 37.5 °C and pH 5.8 and pH 2 respectively(8).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that methenamine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.7X10-10 atm-cu m/mole(SRC), derived from its vapor pressure, 6.1X10-4 mm Hg(4), and water solubility, 3.02X10+5 mg/L(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow of -2.18(7) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Various biolodegradation screening studies have observed between 28-100% degradation of methenamine(8) suggesting that biodegradation is an important environmental fate process in soil(SRC). However, part (or most) of the degradation may be explained by hydrolysis to form formaldehyde and ammonia followed by biodegradation with the degradation rate increasing with acidity(8). Aqueous hydrolysis half-lives of 13.8 hours and 1.6 hours have been measured at 37.5 °C and pH 5.8 and pH 2 respectively(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), methenamine, which has a vapor pressure of 6.1X10-4 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase methenamine 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 45 minutes(SRC), calculated from its rate constant of 5.1X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase methenamine may be removed from the air by wet and dry deposition(SRC).

AEROBIC: In a closed bottle test using a secondary activated sludge inoculum, methenamine was found to be readily biodegradable with 70% biodegraded after 28 days(1). Methenamine was categorized as a synthetic organic chemical unlikely to be removed during biological sewage treatment, even after prolonged exposure of the biota(2). In a 5-day BOD test using a sewage seed, methenamine reached 2.02% of its theoretical BOD(3). Using an activated sludge inoculum, up to 87% removal of methenamine was observed after a 28 day incubation period(4). Methenamine was not degraded in the SCAS test, but it was degraded during 28-day die-away tests(5); no rates were given(SRC). Methenamine, present at 30 mg/L, reached 22% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 100 mg/L in the Japanese MITI test(6); degradation based on TOC and other parameters was 48% suggesting an abiotic hydrolysis component of the degradation(SRC). Methenamine was degraded in various screening tests (>70% DOC, >60% ThoD), but not in activated sludge simulation tests (<25% DOC removal)(7); it was suggested that methenamine would undergo hydrolysis or auto-oxidation in the 28-day screening tests to form biodegradable products, which are not produced in sufficient quantity in 3-hour simulation tests(7). It was observed that methenamine could inhibit degradation, by lowering microbial populations, in both sewage and activated sludge tests depending on concentration(8). Various biological screening studies have observed between 28-100% degradation of methenamine(9); part (or most) of the degradation can be explained by hydrolysis to form formaldehyde and ammonia followed by biodegradation(9); the degradation rate increases with acidity(9).

The rate constant for the vapor-phase reaction of methenamine with photochemically-produced hydroxyl radicals has been estimated as 5.1X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 45 minutes at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Methenamine hydrolyzes in aqueous solution to yield ammonia and formaldehyde(2). The kinetics of hydrolysis of methenamine were studied in citrate-phosphate buffers between pH 2.0 and 7.4 at 37.5 degrees(3); the conversion of methenamine to formaldehyde was found to be pH dependent in the buffers of constant ionic strength, with the reaction half-life decreasing from 13.8 hr at pH 5.8 to 1.6 hr at pH 2.0(3). Using these hydrolysis data, the half-life was extrapolated to as high as 160 days at pH 7.0 and 30 °C(2). Methenamine was reported to hydrolyze rapidly in water at pH 3 or 7 with a the half-life slightly over 1 day at both pHs(4). In a semi-continuous activated sludge system, methenamine removal was 1.1, 18.2, 25.5, 33.6, 41.3, and 52.5% after 5, 10, 15, 20, 30, and 50 days, respectively(5); removal was attributed to acid hydrolysis of methenamine to formaldehyde and ammonia followed by biodegradation of these two compounds(5). Dirct photolysis data were not available(SRC, 2016).

An estimated BCF of 3 was calculated in fish for methenamine(SRC), using a log Kow of -2.18(1) and a regression-derived equation(2). According to a classification scheme(2), 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 for methenamine can be estimated to be about 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that methenamine is expected to have very high mobility in soil(SRC). The pKa of methenamine is 4.89(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The Henry's Law constant for methenamine is estimated as 3.7X10-10 atm-cu m/mole(SRC) derived from its vapor pressure, 6.1X10-4 mm Hg(1), and water solubility, 3.02X10+5 mg/L(2). This Henry's Law constant indicates that methenamine is expected to be essentially nonvolatile from water surfaces(3). Methenamine's estimated Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Methenamine is not expected to volatilize from dry soil surfaces(SRC) based on its vapor pressure.

Methenamine was identified as a volatile organic compound emitted from various types of furniture coatings(1).

Methenamine was not detected in Korean retail provolone cheese, glass noodle and tofu snack (detection limit 0.3-1.0 mg/kg)(1).

Methenamine was tentatively identified in Korean salt-fermented anchovy (Engraulis japonica) paste, hair tail (Trichiurus japonica) viscera paste and shrimp (Acetes chimensis) paste at concentrations of 1,540, 3,820, and 3,990 ng/g, respectively(1).

Methenamine is excreted into breast milk.

Mean emission factors for methenamine from smoldering duff, self-sustained smoldering duff, and smoldering humus were 0.28, 0.02, and 0.059 g/kg(1).

According to the 2012 TSCA Inventory Update Reporting data, 18 reporting facilities estimate the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of methenamine in the United States may be as low as <10 workers and as high as 500-999 workers per plant; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 188,300 workers (40,283 of these are female) are potentially exposed to methenamine in the US(1). Occupational exposure to methenamine may occur through inhalation and dermal contact with this compound at workplaces where methenamine is produced or used(SRC). Monitoring and use data indicate that the general population may be exposed to methenamine via inhalation and dermal contact with consumer products containing methenamine(SRC). The general public exposure to methenamine may also be by direct medical treatment(SRC).

The main route of potential consumer exposure to methenamine is assumed to be via dermal contact(1). Exposure of consumers to methenamine results from the use of cosmetics containing the substance as a preservative (maximum allowed concentration 0.15%) and in addition, from the use of solid fuel tablets(1). Oral exposure may result from the intake of foods containing methenamine food additives(1,2). Oral exposure will result from intake of urinary antibacterial agents containing methenamine(1). Estimated exposure of the Finnish population to methenamine (as a food additive) was reported as 65 ug/day(2). Geometric mean methenamine air concentrations of 0.3 and 0.6 mg/cu m were detected in personal air sampling of shift-leaders and baggers, respectively, at a methenamine producing chemical plant(3). Primary routes of occupational exposure would be skin or eye contact with powder and inhalation of the dust(4).

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Product: Burn in a chemical incinerator equipped with an afterburner and scrubber but exert extra care in igniting as this material is highly flammable. Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

/GUIDE 133 FLAMMABLE SOLIDS/ Fire or Explosion: Flammable/combustible material. May be ignited by friction, heat, sparks or flames. Some may burn rapidly with flare burning effect. Powders, dusts, shavings, borings, turnings or cuttings may explode or burn with explosive violence. Substance may be transported in a molten form at a temperature that may be above its flash point. May re-ignite after fire is extinguished.

/GUIDE 133 FLAMMABLE SOLIDS/ Health: Fire may produce irritating and/or toxic gases. Contact may cause burns to skin and eyes. Contact with molten substance may cause severe burns to skin and eyes. Runoff from fire control may cause pollution.

/GUIDE 133 FLAMMABLE SOLIDS/ Public Safety: CALL Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate telephone number listed on the inside back cover. As an immediate precautionary measure, isolate spill or leak area for at least 25 meters (75 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas.

/GUIDE 133 FLAMMABLE SOLIDS/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Structural firefighters' protective clothing will only provide limited protection.

For more DOT Emergency Guidelines (Complete) data for METHENAMINE (8 total), please visit the HSDB record page.

UN 1328; Hexamethylenetetramine

IMO 4.1; Hexamethylenetetramine

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. Hexamethylenetetramine is included on the dangerous goods list.

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. Hexamethylenetetramine is included on the dangerous goods list.

Flammable Solid

Symbol: F, Xn; R: 11-42/43; S: (2)-16-22-24-37

UN Hazard Class: 4.1; UN Pack Group: III