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Annex II Entry 1504 CMR30/07/2020

Piperazine

Piperazine is listed in Annex II as a prohibited substance for cosmetic products placed on the EU market.

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Prohibited substance— Annex II, EU Regulation 1223/2009
Entry: 1504
CMR

Chemical identity and properties

PubChem 2D chemical structure for CAS 110-85-0
CAS 110-85-0PubChem CID 4837

Piperazine

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. — CAMEO Chemicals

IUPAC name
piperazine
Molecular formula
C4H10N2
Molecular weight
86.14 g/mol
Exact mass
86.084398327 Da
XLogP3
-1.5
Topological polar surface area
24.1 Ų
Hydrogen-bond donors
2
Hydrogen-bond acceptors
2
Covalent units
1
Defined stereocentres
0

Also known as

Diethylenediamine1,4-DiazacyclohexaneHexahydropyrazinePiperazinAntirenPiperazidineDiethyleneimineDispermine
16 more reported names
LumbricalPipersolEraverm1,4-PiperazineWurmirazinUvilonPiperazine, anhydrousWorm-A-Ton1,4-DiethylenediaminePyrazine hexahydrideHexahydro-1,4-diazinePyrazine, hexahydro-Piperazine (USP)NSC-4741RTM4PAL0VPiperazine [USP]
Open full PubChem recordPubChem annotations3D structure image
External database identifiers

Evidence from additional scientific databases

NIH PubChem PUG-View
Exact identifier match4837

Attributed physical-property, hazard, environmental and use annotations.

  • First Aid: 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) shou Source: CAMEO Chemicals
  • ERG2024, Guide 153 (Piperazine): 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, Source: Emergency Response Guidebook (ERG)
  • Signal: Danger Source: Regulation (EC) No 1272/2008 of the European Parliament and of the Council
  • GHS Hazard Statements: 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] Source: Regulation (EC) No 1272/2008 of the European Parliament and of the Council
  • Precautionary Statement Codes: 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) Source: Regulation (EC) No 1272/2008 of the European Parliament and of the Council
  • Note: This chemical does not meet GHS hazard criteria for 0.1% (1 of 768) of reports. Source: European Chemicals Agency (ECHA)
  • Signal: Danger Source: European Chemicals Agency (ECHA)
  • GHS Hazard Statements: 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] Source: European Chemicals Agency (ECHA)
  • Precautionary Statement Codes: 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) Source: European Chemicals Agency (ECHA)
  • ECHA C&L Notifications Summary: 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. Source: European Chemicals Agency (ECHA)
  • Signal: Danger Source: NITE-CMC
  • GHS Hazard Statements: H312: Harmful in contact with skin [Warning Acute toxicity, dermal]; H314: Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]; H317: May cause an allergic skin reaction [Warning Sensitization, Skin]; H318: Causes serious eye damage [Danger Serious eye damage/eye irritation]; H332: Harmful if inhaled [Warning Acute toxicity, inhalation]; H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]; 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] Source: NITE-CMC
  • Precautionary Statement Codes: 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) Source: NITE-CMC
  • GHS Hazard Statements: H302: Harmful if swallowed [Warning Acute toxicity, oral]; H312: Harmful in contact with skin [Warning Acute toxicity, dermal]; H314: Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]; H317: May cause an allergic skin reaction [Warning Sensitization, Skin]; H318: Causes serious eye damage [Danger Serious eye damage/eye irritation]; H334: May cause allergy or asthma symptoms or breathing difficulties if inhaled [Danger Sensitization, respiratory]; H371: May cause damage to organs [Warning Specific target organ toxicity, single exposure]; H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure] Source: NITE-CMC
  • NFPA Health Rating: 2 - Materials that, under emergency conditions, can cause temporary incapacitation or residual injury. Source: Hazardous Substances Data Bank (HSDB)
  • NFPA Fire Rating: 2 - Materials that must be moderately heated or exposed to relatively high ambient temperatures before ignition can occur. Materials would not under normal conditions form hazardous atmospheres with air, but under high ambient temperatures or under moderate heating could release vapor in sufficient quantities to produce hazardous atmospheres with air. Source: Hazardous Substances Data Bank (HSDB)
  • NFPA Instability Rating: 0 - Materials that in themselves are normally stable, even under fire conditions. Source: Hazardous Substances Data Bank (HSDB)
  • Environmental Bioconcentration: 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). Source: Hazardous Substances Data Bank (HSDB)
  • Environmental Fate: 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). Source: Hazardous Substances Data Bank (HSDB)
  • Environmental Fate: 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). Source: Hazardous Substances Data Bank (HSDB)
  • Environmental Fate: 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). Source: Hazardous Substances Data Bank (HSDB)

Mapped by: Existing checksum-valid CAS to unique PubChem CID match. Retrieved: 2026-08-31. Open source record

Scientific classifications and hazard annotations provide context and do not replace the market-specific regulatory decision shown above.

Additional source coverage and match status
SourceResultChecked
NIH PubChem PUG-ViewExact match2026-08-31

A recorded no-match is useful evidence that the source was checked; it is not a claim that the substance does not exist elsewhere.

Retrieved from NIH PubChem on 2026-09-02 by checksum-valid CAS matching. Chemical properties do not replace the regulatory decision on this page.

Record details

Chemical name

Piperazine

Chemical / IUPAC name

Piperazine

Regulatory information

Regulation

(EU) 2019/831

See every entry this act set

CMR

CategoryCarcinogenicMutagenicReprotoxic
Cat. 2——✓

Key data

CAS
110-85-0
EC
203-808-3
Annex
II
Entry number
1504

Direct matches are limited for this record, so nearby entries from Annex II are shown as well.

Annex II 1503
Nearby record in the same annex

Cyclohexylamine

CAS: 108-91-8
EC: 203-629-0
Annex II 1505
Nearby record in the same annex

Hydroxylamine

CAS: 7803-49-8
EC: 232-259-2

What Annex II means for Piperazine

Piperazine is listed as a prohibited substance under Annex II of EU Cosmetics Regulation 1223/2009 and must not be intentionally added. Article 17 separately addresses unintended small quantities that are technically unavoidable under good manufacturing practice and compatible with the Article 3 safety requirement.

Formulators must screen their ingredients and raw materials to ensure none contain this substance. Suppliers should provide documentation confirming absence when requested.

The page also surfaces 12 related annex records with overlapping identifiers, annex logic or naming patterns.

Compliance checklist

  • Verify this substance is absent from all raw materials and finished formulations.
  • Request absence confirmation or CoA from raw material suppliers.
  • Document the screening result in the Product Information File (PIF).
  • This substance has CMR classification. Review the CMR table above and verify current Annex II/III status before use.

Frequently asked questions

Yes. Piperazine is listed in Annex II of EU Cosmetics Regulation 1223/2009 and is prohibited as an intentionally added cosmetic ingredient. Article 17 provides a narrow exception for unintended small quantities that are technically unavoidable under good manufacturing practice, provided the product remains safe under Article 3.

CAS 110-85-0 is the unique numerical identifier assigned to Piperazine by the Chemical Abstracts Service. In cosmetic compliance work, the CAS number is used to cross-reference the substance across regulatory databases, raw material specifications and safety assessment reports. Multiple EU annex entries may share the same CAS number if the same substance appears under different conditions or in different annexes.

Piperazine has a CMR (carcinogenic, mutagenic or reprotoxic) classification under EU CLP Regulation. Under Article 15 of EU Cosmetics Regulation 1223/2009, CMR substances of category 1A or 1B are prohibited in cosmetics unless specifically permitted. Category 2 CMR substances may be used only if assessed safe by the SCCS. Always verify current annex status and any applicable derogations before use.

Use the INCI Checker tool on this site to paste your full ingredient list (INCI) and scan it against all Annex II–VI entries. The tool highlights any ingredients that match restricted, prohibited or allergen-flagged records. This is useful for rapid compliance screening of finished product formulas or raw material declarations.
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Source note for Annex II record Piperazine

This page summarizes one Annex II record for Piperazine from public European Commission cosmetic materials and adds linked inventory or identifier matches when available.

Use this record page to review Annex II conditions for Piperazine, but confirm any final regulatory decision against the current official annex wording and source files.

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