piperazine

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

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

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

H361fd: Suspected of damaging fertility; Suspected of damaging the unborn child [Warning Reproductive toxicity]

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

This chemical does not meet GHS hazard criteria for 0.1% (1 of 768) of reports.

H228 (34.6%): Flammable solid [Danger Flammable solids]

H314 (99.9%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

H317 (99.7%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H318 (39.7%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

H334 (99.7%): May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]

H361 (77.3%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H361fd (23.4%): Suspected of damaging fertility; Suspected of damaging the unborn child [Warning Reproductive toxicity]

P203, P210, P233, P240, P241, P260, P261, P264, P264+P265, P271, P272, P280, P284, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P318, P321, P333+P317, P342+P316, P362+P364, P363, P370+P378, P403, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 768 reports by companies from 32 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 1 of 768 reports by companies.

There are 31 notifications provided by 767 of 768 reports by companies with hazard statement code(s).

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.

H312: Harmful in contact with skin [Warning Acute toxicity, dermal]

H318: Causes serious eye damage [Danger Serious eye damage/eye irritation]

H332: Harmful if inhaled [Warning Acute toxicity, inhalation]

H335: May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

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

H370: Causes damage to organs [Danger Specific target organ toxicity, single exposure]

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

H402: Harmful to aquatic life [Hazardous to the aquatic environment, acute hazard]

P203, P233, P260, P261, P264, P264+P265, P270, P271, P272, P273, P280, P284, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P308+P316, P316, P317, P318, P319, P321, P333+P317, P342+P316, P362+P364, P363, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

H302: Harmful if swallowed [Warning Acute toxicity, oral]

H371: May cause damage to organs [Warning Specific target organ toxicity, single exposure]

P233, P260, P261, P264, P264+P265, P270, P271, P272, P280, P284, P301+P317, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P308+P316, P316, P317, P319, P321, P330, P333+P317, P342+P316, P362+P364, P363, P403, P405, and P501 (click each P-code to see the statement)

H373: May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P203, P233, P260, P261, P264, P270, P271, P272, P280, P284, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P308+P316, P316, P318, P319, P321, P333+P317, P342+P316, P362+P364, P363, P403, P405, and P501 (click each P-code to see the statement)

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

Remove contaminated clothes. Rinse skin with plenty of water or shower for at least 15 minutes. 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. Do NOT induce vomiting. 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:

· For corrosives, in case of contact, immediately flush skin or eyes with running water for at least 30 minutes. Additional flushing may be required.

· 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 153 [Substances - Toxic and/or Corrosive (Combustible)]:

SMALL FIRE: Dry chemical, CO2 or water spray.

LARGE FIRE: Dry chemical, CO2, alcohol-resistant foam or water spray. If it can be done safely, move undamaged containers away from the area around the fire. Dike runoff from fire control for later disposal.

FIRE INVOLVING TANKS, RAIL TANK CARS OR HIGHWAY TANKS: Fight fire from maximum distance or use unmanned master stream devices or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. 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, powder, alcohol-resistant foam, carbon dioxide.

Piperazine is a combustible liquid. Use dry chemical, carbon dioxide, water spray, or alcohol foam extinguishers. Piperazine may burn, but does not readily ignite. Extinguish fire using an agent suitable for type of surrounding fire. Poisonous gases including nitrogen oxides and hydrogen chloride (hydrochloride) are produced in fire. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Notify local health and fire officials and pollution control agencies. Containers may explode in fire. From a secure, explosion-proof location, use water spray to cool exposed containers. If cooling streams are ineffective (venting sound increases in volume and pitch, tank discolors, or shows any signs of deforming), withdraw immediately to a secure position. If employees are expected to fight fires, they must be trained and equipped in OSHA 1910.156.

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. Apply water from as far a distance as possible. Use water spray to knock-down vapors.

· 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.

· Ventilate closed spaces before entering, but only if properly trained and equipped.

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

· Do not touch damaged containers or spilled material unless wearing appropriate protective clothing.

· Stop leak if you can do it without risk.

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

· Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers.

· DO NOT GET WATER INSIDE CONTAINERS.

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

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 the immediate precautionary measure distance, in the downwind direction, as necessary.

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 in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.

· For highlighted materials: see Table 1 - Initial Isolation and Protective Action Distances.

· For non-highlighted materials: increase the immediate precautionary measure distance, in the downwind direction, as necessary.

· 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: chemical protection suit including self-contained breathing apparatus. Do NOT let this chemical enter the environment. Ventilation. 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.

Evacuate persons not wearing protective equipment from area of spill or leak until clean-up is complete. Remove all ignition sources. Collect powdered material in the most convenient and safe manner and deposit in sealed containers. Ventilate area after clean-up is complete. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or contaminated runoff enters waterways, notify downstream users of potentially contaminated waters. Contact your Department of Environmental Protection or your regional office of the federal EPA for specific recommendations. If employees are required to clean-up spills, they must be properly trained and equipped. OSHA 1910.120(q) may be applicable.

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.

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary.

Personnel protection: Avoid breathing vapors. Keep upwind. ... Avoid bodily contact with the material. ... Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water. If contact with the material anticipated, wear appropriate chemical protective clothing.

The worker should immediately wash the skin when it becomes contaminated.

Work clothing that becomes wet or significantly contaminated should be removed and replaced.

For more Preventive Measures (Complete) data for PIPERAZINE (6 total), please visit the HSDB record page.

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

ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area. Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. (ERG, 2024)

Separated from strong acids, strong oxidants, acid anhydrides, metals and food and feedstuffs. Dry. Well closed.

Piperazine must be stored to avoid contact with oxidizers (such as perchlorates, peroxides, permanganates, chlorates, and nitrates) since violent reactions occur. . Sources of ignition such as smoking and open flames are prohibited where piperazine is used, handled, or stored in a manner that could create a potential fire or explosion hazard. Store in tightly closed containers in a cool, well vented area away form oxidizers. Where possible, automatically transfer material from drums or other storage containers to process containers. Metal containers involving the transfer of this chemical should be grounded and bonded. Wherever this chemical is used, handled, manufactured, or stored, use explosion-proof electrical equipment and fittings.

Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer. /Piperazine adipate granules for oral solution/

Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer. Protect from freezing. /Piperazine adipate oral suspension/

Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F). Store in a tight container.

For more Storage Conditions (Complete) data for PIPERAZINE (6 total), please visit the HSDB record page.

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

· Wear chemical protective clothing that is specifically recommended by the manufacturer when there is NO RISK OF FIRE.

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

0.10 [mg/m3]

31 [mg/m3]

190 [mg/m3]

0.03 [ppm], inhalable fraction and vapor, measured as piperazine

8 hr Time Weighted Avg (TWA): 5 mg/cu m. /Piperazine dihydrochloride/

Excursion Limit Recommendation: Excursions in worker exposure levels may exceed 3 times the TLV-TWA for no more than a total of 30 minutes during a work day, and under no circumstances should they exceed 5 times the TLV-TWA, provided that the TLV-TWA is not exceeded. /Piperazine dihydrochloride/

0.03 ppm as TWA; (SEN); A4 (not classifiable as a human carcinogen).

0.1 mg/m

sensitization of respiratory tract and skin (SAH).

Small Fire

· Dry chemical, CO2 or water spray.

Large Fire

· Dry chemical, CO2, alcohol-resistant foam or water spray.

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

· Dike runoff from fire control for later disposal.

Fire Involving Tanks, Rail Tank Cars or Highway Tanks

· Fight fire from maximum distance or use unmanned master stream devices or monitor nozzles.

· Do not get water inside containers.

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

· 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.

No indication can be given about the rate at which a harmful concentration of this substance in the air is reached on evaporation at 20 °C.

The substance is corrosive to the eyes, skin and respiratory tract. Corrosive on ingestion. Inhalation may cause lung oedema, but only after initial corrosive effects on eyes and/or airways have become manifest. Ingestion could cause effects on the nervous system. This may result in impaired functions and unconsciousness.

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

A tolerance of 0.1 part per million piperazine base is established for edible tissues of poultry and swine.

In the European Union, maximum residue limits of piperazine have been established as follows: Porcine - 400 ug/kg in muscle, 800 ug/kg in skin + fat, 2,000 ug/kg in liver, and 1,000 ug/kg in kidney; Chicken - 2,000 ug/kg in eggs.

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

Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer when there is NO RISK OF FIRE. Structural firefighters' protective clothing provides thermal protection but only limited chemical protection. (ERG, 2024)

Wear appropriate personal protective clothing to prevent skin contact.

Wear appropriate eye protection to prevent eye contact.

Eyewash fountains should be provided in areas where there is any possibility that workers could be exposed to the substance; this is irrespective of the recommendation involving the wearing of eye protection.

Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is a possibility of exposure. [Note: It is intended that these facilities provide a sufficient quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, a deluge shower should be readily available, whereas in others, the availability of water from a sink or hose could be considered adequate.]

NO open flames. Above 65 °C use a closed system and ventilation.

PREVENT DISPERSION OF DUST! AVOID ALL CONTACT! IN ALL CASES CONSULT A DOCTOR!

Avoid inhalation of dust. Use ventilation, local exhaust or breathing protection.

Protective gloves. Protective clothing.

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

Needle-like white or colorless crystals. Shipped as a solid or suspended in a liquid medium. Very corrosive to skin, eyes and mucous membranes. Solid turns dark when exposed to light. Flash point 190 °F. Used as a corrosion inhibitor and as an insecticide.

Large Crystals; CBI; Liquid

Colorless solid, hygroscopic, with a pungent odor; [ICSC]

HYGROSCOPIC COLOURLESS CRYSTALS OR WHITE FLAKES WITH PUNGENT ODOUR.

Colourless to yellow solid; Salty taste

Plates or leaflets from ethanol

WHITE TO SLIGHTLY OFF-WHITE LUMPS OR FLAKES

Colorless, transparent, needle-like crystals

Typical amine odor

AMMONIACAL ODOR

Salty taste

295 °F at 760 mmHg (NTP, 1992)

146 °C @760 [mm Hg]

223 °F (NTP, 1992)

MP: 82-83 °C /Piperazine hydrochloride monohydrate/

190 °F (NTP, 1992)

107 °C (Cleveland Open Cup)

Very soluble (NTP, 1992)

Mol wt 184.13. Minute crystals. Very slightly sol in water. pH of saturated aq soln 6.5 /Phosphate/

Freely soluble in glycerol, glycols; one gram dissolves in 2 ml of 95% alcohol. Insoluble in ether.

Very soluble in chloroform.

Readily soluble in methanol, but only slightly soluble in benzene and heptane.

Freely soluble in water.

3.71e+02 g/L

Solubility in water, g/100ml at 20 °C: 15

Soluble in water

Soluble (in ethanol)

1.1 at 68 °F (NTP, 1992) - Denser than water; will sink

1.1 g/cu cm

1.1 g/cm³

Relative density of the vapour/air-mixture at 20 °C (air = 1): 1

1.45 @ 113°C

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

3.0 (air = 1)

Relative vapor density (air = 1): 3

0.16 [mmHg]

Vapor pressure = 2.6372X10+4 Pa @ 379.15 deg K

0.16 mm Hg at 20 °C

Vapor pressure, Pa at 20 °C: 21

0.16 [mm Hg] @20 °C

Flammable. Absorbs water and carbon dioxide from air. Soluble in water.

Amines, Phosphines, and Pyridines

PIPERAZINE neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Absorbs carbon dioxide from the air, which can cause dry crystals to seem to melt. May generate hydrogen, a flammable gas, in combination with strong reducing agents such as hydrides. This compound is sensitive to light; it absorbs water and carbon dioxide from air. This compound may be corrosive to aluminum, magnesium and zinc. (NTP, 1992).

Violent reaction with strong oxidizers and dicyanofurazan. Incompatible with nitrogen compounds, carbon tetrachloride. Attacks aluminum, copper, nickel, magnesium, and zinc.

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

Burning sensation. Cough. Sore throat. Shortness of breath. Laboured breathing. Wheezing.

Skin burns. Pain. Blisters.

Redness. Pain. Severe burns.

Burning sensation. Abdominal pain. Nausea. Vomiting. Headache. Weakness. Convulsions. Shock or collapse.

Neurotoxin - Other CNS neurotoxin

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

Dermatotoxin - Skin burns.

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

Asthma - Reversible bronchoconstriction (narrowing of bronchioles) initiated by the inhalation of irritating or allergenic agents.

Toxic Pneumonitis - Inflammation of the lungs induced by inhalation of metal fumes or toxic gases and vapors.

ACGIH Carcinogen - Not Classifiable.

LC50 (mice) = 5,400 mg/m3/2h

LD50 Rat oral 4,900 mg/kg /Piperazine hydrochloride/

LD50 Rat oral 2,050 mg/kg /Piperazine base/

LD50 Mouse oral 6,200 mg/kg /Piperazine hydrochloride/

LD50 Mouse oral 7,000 mg/kg /Piperazine dihydrochloride/

For more Non-Human Toxicity Values (Complete) data for PIPERAZINE (9 total), please visit the HSDB record page.

In mice, doses of about 625 mg piperazine base/kg bw (6,250 mg/kg feed( was administered for 28 weeks together with 0.1% nitrite in the drinking water. After an additional period of 12 weeks on a basal diet without piperazine and nitrite, a 10 fold increase in numbers of lung adenomas vs control numbers was observed. MIce receiving piperazine alone during the same time period showed afterwards no increase in tumor incidence.

In a different study an increased frequency of lung adenomas in mice was seen when oral doses corresponding to 1,250 mg piperazine/kg bw/day plus 5 mg sodium nitrite/kg bw/day or 138 mg piperazine/kg bw/day plus 200 mg sodium nitrite/kg bw/day were given. Doses of 1,250 mg piperazine.kg bw.day plus 1 mg sodium nitrite/kg bw/day did not result in any increased tumor frequency. In rats receiving 30 mg piperazing/kg bw/day plus 70 mg (0.05%) nitrite daily for 75 weeks there was no increase in tumor incidence.

High doses of piperazine may enhance the effects of chlorpromazine and increase the risk of seizures; concurrent use is not recommended.

Pyrantel may antagonize the anthelmintic effect of piperazine; concurrent use is not recommended.

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 needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . 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 ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

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. 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 ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ After treatment of a four-year-old child for 3 days with 100 mg/kg bw piperazine hexahydrate (44 mg/kg b.w. piperazine base), severe asthenia, tottering gait, poor balance, extreme muscular weakness, and EEG changes developed. This first case caused the clinic to investigate all children under treatment with piperazine. In 10 out of 11 children treated with piperazine (hexa) hydrate 80 mg/kg bw (35 mg/kg bw piperazine base) per day for five days, abnormal EEG changes were noted that were similar to those previously described in the literature (i.e. continuous bilateral spikes and polyspikes and high-voltage waves interspaced with slow-wave activity). Only one of the children was reported to suffer from clinical abnormality that could cause confounding (enlarged liver due to chronic cardiac failure). Upon repeated treatment, after normalization of the EEG, of 6 of the children with piperazine hydrate at the same dose together with 1 mg/kg bw prednisone per day the EEG changes either did not appear, or were reported to be less pronounced.[European Commission; EUR 21642 EN European Union Risk Assessment Report Piperazine, Volume 56. Luxembourg: Office for Official Publications of the European Communities (2005). Available from, as of November 15, 2006: http://ecb.jrc.it/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/piperazinereport324.pdf]

/SIGNS AND SYMPTOMS/ Besides asthma, chronic exposure to piperazine has been found to induce chronic bronchitis. The over-all prevalence of bronchitis among the Swedish workers involved in piperazine production and processing was found to be around 16%, exhibiting a clear dose-response relationship.[European Commission; EUR 21642 EN European Union Risk Assessment Report Piperazine, Volume 56. Luxembourg: Office for Official Publications of the European Communities (2005). Available from, as of November 15, 2006: http://ecb.jrc.it/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/piperazinereport324.pdf]

/SIGNS AND SYMPTOMS/ Transient side effects have been observed which include headaches, nausea, vomiting, diarrhea, lethargy, tremor, incoordination, muscular weakness, urticaria, and vague ocular disturbances. There is a wide range between effective therapeutic and toxic doses. Piperazine (in salt form) has been used without ill effect during pregnancy. /Piperazine salts/[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 2692]

/SIGNS AND SYMPTOMS/ Therapeutic doses do not usually cause adverse effects, but nausea, vomiting, diarrhea, and allergic reactions may develop. With larger doses, as in inadvertent overdosage or when the drug accumulates in the presence of renal insufficiency, muscular incoordination or weakness, vertigo, dysphasia, confusion, and myoclonic contraction have been reported. These effect usually disappear when the drug is discontinued. Piperazine citrate may induce or exacerbate epileptic seizures in predisposed patients. /Piperazine citrate/[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 1754]

For more Human Toxicity Excerpts (Complete) data for PIPERAZINE (17 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ The administration of 110 mg piperazine (as the adipate) per kg body weight orally to rats for 8 weeks did not result in any significant pathological changes. /Piperazine adipate/[European Commission; EUR 21642 EN European Union Risk Assessment Report Piperazine, Volume 56. Luxembourg: Office for Official Publications of the European Communities (2005). Available from, as of November 15, 2006: http://ecb.jrc.it/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/piperazinereport324.pdf]

/LABORATORY ANIMALS: Acute Exposure/ Tested full strength by application of drop to rabbits eyes, it has caused severe injury, graded 9 on scale of 1 to 10 after 24 hr. ... No injury was caused by 0.2 molar aq soln at ph 7.5 dropped continuously on rabbit eyes for 10 min after mechanical removal of corneal epithelium to permit penetration.[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 741]

/LABORATORY ANIMALS: Acute Exposure/ Oral administration of half a 275 mg tablet of piperazine citrate on 2 successive days to an undersized 1 yr old domestic cat induced severe neurological symptoms, including epileptiform seizures. /Piperazine citrate/[Hartigan PJ et al; IR Vet J; 30 (12): 188 (1976)]

/LABORATORY ANIMALS: Acute Exposure/ In a GLP study 4 pigs received a dose of 300 mg piperazine dihydrochloride/ kg bw by oral gavage for three consecutive days. Two male pigs received 1,500 mg/kg bw/day (5 times the recommended dosage) and two more male pigs received 3,000 mg/kg bw/day (10 times). All pigs were 11 to 13 weeks old. The pigs in the high and intermediate dosage group died. These animals showed adverse signs within 0.5 hr after the first administration predominantly related to the CNS as vomiting, inappetence, abnormal respiration, ataxia, prostration, muscle tremors, convulsions, bright yellow urine and death. All dead animals showed a vacuolar tubular nephropathy. In the 300 mg/kg dosage group animals showed transient discoloration of urine (bright yellow), one male was inappetent, shivering and subdued. The severe unexpected effects were attributed to the administration of a bolus instead of administration by drinking water. /Piperazine dihydrochloride/[European Medicines Agency (EMEA), The European Agency for the Evaluation of Medicinal Products, Veterinary Medicines Evaluation Unit, Committee for Veterinary Medicinal Products; Piperazine, Summary Report (3). EMEA/MRL/807/01-Final (November 2001). Available from, as of November 15, 2006: http://www.ema.europa.eu/ema/index.jsp?curl=pages/document_library/landing/document_library_search.jsp&murl=menus/document_library/document_library.jsp&mid]

For more Non-Human Toxicity Excerpts (Complete) data for PIPERAZINE (25 total), please visit the HSDB record page.

Piperazine has been reported to induce hemolytic anaemia in an individual deficient in glucose-6-phosphate dehydrogenase.

This substance may be hazardous to the environment. Special attention should be given to fish.

Piperazine's production and use as an anthelmintic in human and veterinary medicine and as an intermediate for dyes, corrosion inhibitors, rubber vulcanization accelerators, insecticides, and surfactants may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.16 mm Hg at 20 °C indicates piperazine will exist solely as a vapor in the atmosphere. Vapor-phase piperazine 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 2.3 hours. Piperazine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, piperazine is expected to have very high mobility based upon an estimated Koc of 3.6. Measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen), indicate that piperazine will exist primarily as a cation 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 because ionic compounds do not volatilize. Piperazine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Piperazine may biodegrade in soil or water based on greater than 51% biodegradation measured after 28 days in an artificial river water TOC die-away test; however, only 1.4% degradation occurred after 14 days during a MITI screening test. If released into water, piperazine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc; however adsorption may be attenuated since cations adsorb more strongly to suspended solids and sediments than their neutral counterparts. Volatilization from water surfaces is not expected to be an important fate process since ionic compounds do not volatilize. A BCF of less than 0.3 to 0.9 suggests bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to piperazine may occur through inhalation and dermal contact with this compound at workplaces where piperazine is produced or used. Monitoring data indicate that the general population may be exposed to piperazine via inhalation of ambient air. Individuals will be exposed to piperazine if they are administered this substance as a drug. (SRC)

Piperazine's production and use as an anthelmintic in human and veterinary medicine and as an intermediate for dyes, corrosion inhibitors, rubber vulcanization accelerators, insecticides, and surfactants(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3.6(SRC), determined from a log Kow of -1.50(2) and a regression-derived equation(3), indicates that piperazine is expected to have very high mobility in soil(SRC). Measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen)(4) indicate that piperazine will exist primarily in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of piperazine from moist soil surfaces is not expected to be an important fate process(SRC) since cations do not volatilize. Piperazine is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.16 mm Hg(6). Piperazine may biodegrade in soil based on greater than 51% biodegradation measured after 28 days in a artificial river water total organic carbon (TOC) die-away test; however, only 1.4% degradation occurred after 14 days during a MITI screening test(7,8).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3.6(SRC), determined from a log Kow of -1.50(2) and a regression-derived equation(3), indicates that piperazine is not expected to adsorb to suspended solids and sediment(SRC). However, measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen)(4) indicate piperazine will exist almost entirely in the cation form at pH values of 5 to 9 and cations adsorb to suspended solids and sediment more strongly than their neutral counterparts(5). Volatilization of piperazine from water surfaces is not expected to be an important fate process since cations do not volatilize. According to a classification scheme(6), a BCF range of less than 0.3-0.9(7) suggests the potential for bioconcentration in aquatic organisms is low(SRC). Piperazine may biodegrade in water based on greater than 51% biodegradation measured after 28 days in a artificial river water total organic carbon (TOC) die-away test; however, only 1.4% degradation occurred after 14 days during a MITI screening test(7,8).

This substance may be hazardous to the environment. Special attention should be given to fish.

Piperazine's production and use as an anthelmintic in human and veterinary medicine and as an intermediate for dyes, corrosion inhibitors, rubber vulcanization accelerators, insecticides, and surfactants may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.16 mm Hg at 20 °C indicates piperazine will exist solely as a vapor in the atmosphere. Vapor-phase piperazine 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 2.3 hours. Piperazine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, piperazine is expected to have very high mobility based upon an estimated Koc of 3.6. Measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen), indicate that piperazine will exist primarily as a cation 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 because ionic compounds do not volatilize. Piperazine is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Piperazine may biodegrade in soil or water based on greater than 51% biodegradation measured after 28 days in an artificial river water TOC die-away test; however, only 1.4% degradation occurred after 14 days during a MITI screening test. If released into water, piperazine is not expected to adsorb to suspended solids and sediment based upon the estimated Koc; however adsorption may be attenuated since cations adsorb more strongly to suspended solids and sediments than their neutral counterparts. Volatilization from water surfaces is not expected to be an important fate process since ionic compounds do not volatilize. A BCF of less than 0.3 to 0.9 suggests bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to piperazine may occur through inhalation and dermal contact with this compound at workplaces where piperazine is produced or used. Monitoring data indicate that the general population may be exposed to piperazine via inhalation of ambient air. Individuals will be exposed to piperazine if they are administered this substance as a drug. (SRC)

Piperazine's production and use as an anthelmintic in human and veterinary medicine and as an intermediate for dyes, corrosion inhibitors, rubber vulcanization accelerators, insecticides, and surfactants(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3.6(SRC), determined from a log Kow of -1.50(2) and a regression-derived equation(3), indicates that piperazine is expected to have very high mobility in soil(SRC). Measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen)(4) indicate that piperazine will exist primarily in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of piperazine from moist soil surfaces is not expected to be an important fate process(SRC) since cations do not volatilize. Piperazine is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.16 mm Hg(6). Piperazine may biodegrade in soil based on greater than 51% biodegradation measured after 28 days in a artificial river water total organic carbon (TOC) die-away test; however, only 1.4% degradation occurred after 14 days during a MITI screening test(7,8).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3.6(SRC), determined from a log Kow of -1.50(2) and a regression-derived equation(3), indicates that piperazine is not expected to adsorb to suspended solids and sediment(SRC). However, measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen)(4) indicate piperazine will exist almost entirely in the cation form at pH values of 5 to 9 and cations adsorb to suspended solids and sediment more strongly than their neutral counterparts(5). Volatilization of piperazine from water surfaces is not expected to be an important fate process since cations do not volatilize. According to a classification scheme(6), a BCF range of less than 0.3-0.9(7) suggests the potential for bioconcentration in aquatic organisms is low(SRC). Piperazine may biodegrade in water based on greater than 51% biodegradation measured after 28 days in a artificial river water total organic carbon (TOC) die-away test; however, only 1.4% degradation occurred after 14 days during a MITI screening test(7,8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), piperazine, which has a vapor pressure of 0.16 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase piperazine 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 2.3 hours(SRC), calculated from its rate constant of 1.7X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Piperazine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(4).

AEROBIC: Piperazine, present at 100 mg/L, reached 1.4% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/L and the Japanese MITI test(1). In a total organic carbon (TOC) die-away test, piperazine, at an initial concentration of 36 ppm, was degraded by greater than 51% after 28 days in 3 out of 4 artificial river water inocula containing river water microorganisms collected in both spring and autumn(2). Only 0-15% biodegradation occured after 28 days in the fourth inoculum, which contained river water microorganisms collected during the spring(2). Piperazine, at 20 ppm, was degraded by 20% in river water and 77% in sea water after 3 days using the cultivation method(3).

ANAEROBIC: Piperazine at a concentration of 1.0 mM and incubated in freshwater sediment, activated sludge, and estuarine sediment was not degraded after 6 months under denitrifying, sulfate reducing, or methanogenic conditions(1).

Piperazine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Piperazine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(1).

BCF values less than 0.3 to 0.9 and less than 3.9 were measured using orange-red killifish (Oryzias latipes) which were exposed to 1 and 0.1 ppm, respectively, over an 8-week period(1). According to a classification scheme(2), these BCF values suggest the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of piperazine is estimated as 3.6(SRC), using a log Kow of -1.50(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that piperazine is expected to have very high mobility in soil. Measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen)(4), indicate that this compound will primarily exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

Measured pKa values of 9.73 (first nitrogen) and 5.33 (second nitrogen) indicate that piperazine will exist primarily as a cation in the environment(1). Volatilization from moist soil or water surfaces is not expected(SRC) since ionic compounds do not volatilize. Piperazine is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.16 mm Hg(2).

An ambient piperazine concentration of 10-60 ng/cu m in air has been reported(1).

URBAN/SUBURBAN: The concentrations of piperazine measured in submicron aerosol (less than 1-2 um) of Pasedina, California were 0.02, 0.02, 0.05, and 0.06 ug/cu m in 1985, 1986, 1987, and 1988, respectively(1). Piperazine was not detected in supermicron aerosol (greater than 1-2 um) samples collected during 1985, 1986, or 1988(1). The concentration measured in supermicron aerosol during 1987 was 0.01 ug/cu m(1).

EXPERIMENTAL: Piperazine is thought to be distributed into breast milk but no definitive information is available.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 8,786 workers (2,609 of these are female) are potentially exposed to piperazine in the US(1). Occupational exposure to piperazine may occur through inhalation and dermal contact with this compound at workplaces where piperazine is produced or used(SRC). Monitoring data indicate that the general population may be exposed to piperazine via inhalation of ambient air(SRC). Individuals will be exposed to piperazine if they are administered this substance as a drug(SRC).

Concentrations of the piperazine metabolite N-mononitrosopiperazine were measured in the urine of 11 male workers exposed to 0.06 to 1.7 mg/cu m piperazine over 12 hours in a chemical manufacturing plant(1). The excretion of N-mononitrosopiperazine was 0.3 to 4.7 ug/24 hours in 5 cases(1). N-mononitrosopiperazine was detected at 0.1 to 0.6 ug/L in the urine of 4 other workers(1). It was not detected in the urine of 2 workers (less than 0.1 ng/ml)(1).

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.

/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.

/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.

/GUIDE 153: SUBSTANCES - TOXIC and/or CORROSIVE (Combustible)/ 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 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.

/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.

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

UN 2579; Piperazine

IMO 8.0; Piperazine

49 356 54; Piperazine

Piperazine requires a shipping label of: "Corrosive." It falls into DOT Hazard Class 8 and Packing Group III.

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.

Corrosive

Symbol: C; R: 34-42/43-52/53; S: (1/2)-22-26-36/37/39-45-61

UN Hazard Class: 8; UN Pack Group: III