Isobutyl nitrite

H225: Highly Flammable liquid and vapor [Danger Flammable liquids]

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

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

H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H350: May cause cancer [Danger Carcinogenicity]

P203, P210, P233, P240, P241, P242, P243, P261, P264, P270, P271, P280, P301+P317, P303+P361+P353, P304+P340, P317, P318, P330, P370+P378, P403+P235, P405, and P501 (click each P-code to see the statement)

H225 (100%): Highly Flammable liquid and vapor [Danger Flammable liquids]

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

H332 (95.9%): Harmful if inhaled [Warning Acute toxicity, inhalation]

H341 (100%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H350 (100%): May cause cancer [Danger Carcinogenicity]

Aggregated GHS information provided per 49 reports by companies from 4 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.

H331: Toxic if inhaled [Danger Acute toxicity, inhalation]

H351: Suspected of causing cancer [Warning Carcinogenicity]

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]

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

P203, P210, P233, P240, P241, P242, P243, P260, P261, P264, P270, P271, P280, P301+P317, P303+P361+P353, P304+P340, P308+P316, P316, P318, P319, P321, P330, P370+P378, P403+P233, P403+P235, P405, and P501 (click each P-code to see the statement)

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

Fresh air, rest. Artificial respiration may be needed. Refer for medical attention.

Rinse and then wash skin with water and soap.

Rinse with plenty of water for several minutes (remove contact lenses if easily possible).

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. Volatile chemicals have a high risk of being aspirated into the victim's lungs during vomiting which increases the medical problems. 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. IMMEDIATELY transport the victim to a hospital. 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)

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Use dry powder, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water.

Excerpt from ERG Guide 131 [Flammable Liquids - Toxic]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area for at least 50 meters (150 feet) in all directions.

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)

Personal protection: self-contained breathing apparatus. Evacuate danger area! Consult an expert! Ventilation. Remove all ignition sources. Collect leaking and spilled liquid in sealable containers as far as possible. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations. Do NOT wash away into sewer.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing 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 protect this chemical from exposure to light. Keep the container tightly closed under an inert atmosphere, and store it in an explosion-proof refrigerator. STORE AWAY FROM SOURCES OF IGNITION. (NTP, 1992)

Fireproof. Separated from acids. Well closed.

Biological Exposure Indices (BEI) [ACGIH] - Methemoglobin in blood = 1.5% of hemoglobin during or at end of shift. [ACGIH]

1.0 [ppm]

(ceiling value): 1 ppm as STEL; A3 (confirmed animal carcinogen with unknown relevance to humans); BEI issued

1 ppm [2000]

A harmful contamination of the air can be reached very quickly on evaporation of this substance at 20 °C.

The substance may cause effects on the blood and cardiovascular system. This may result in cardiac disorders and the formation of methaemoglobin. The effects may be delayed. Medical observation is indicated. Exposure at high levels could cause death.

This substance is possibly carcinogenic to humans.

RECOMMENDED RESPIRATOR: When working with this chemical, wear a NIOSH-approved full face chemical cartridge respirator equipped with the appropriate organic vapor cartridges. If that is not available, a half face respirator similarly equipped plus airtight goggles can be substituted. However, please note that half face respirators provide a substantially lower level of protection than do full face respirators.

RECOMMENDED GLOVE MATERIALS: If this chemical makes direct contact with your gloves, or if a tear, puncture or hole develops, replace them at once.

Glove Type Model Number Thickness Bkthru Time

Viton North F-091 0.41 mm 18 min

Butyl Rubber North B-174 0.69 mm 75 min

Nitrile Edmont 37-155 0.61 mm 91 min

PVA Edmont 29-250 0.53 mm 19 min

PVC Edmont 34-100 0.15 mm 2 min (NTP, 1992)

NO open flames, NO sparks and NO smoking. Closed system, ventilation, explosion-proof electrical equipment and lighting. Do NOT use compressed air for filling, discharging, or handling.

AVOID ALL CONTACT!

Use ventilation, local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear safety spectacles.

Do not eat, drink, or smoke during work. Wash hands before eating.

Isobutyl nitrite is a clear colorless to pale yellow liquid. Boiling point 154.4 °F (68 °C).

Clear colorless to pale yellow liquid; [CAMEO]

COLOURLESS LIQUID.

Clear colorless to pale yellow liquid.

COLORLESS LIQUID

153 °F at 760 mmHg (NTP, 1992)

154.4 °F

-10 °F (NTP, 1992)

less than 1 mg/mL at 66 °F (NTP, 1992)

SLIGHTLY SOLUBLE AND GRADUALLY DECOMPOSED BY WATER; MISCIBLE WITH ALCOHOL

Solubility in water: very poor

0.87 at 72 °F (NTP, 1992) - Less dense than water; will float

0.870 AT 22 °C/4 °C

Relative density (water = 1): 0.87

0.87 at 72 °F

greater than 1 (NTP, 1992) (Relative to Air)

Relative vapor density (air = 1): 3.56

10 mmHg at 68 °F ; 17.80 mmHg at 86 °F (NTP, 1992)

10.0 [mmHg]

Vapor pressure, kPa at 20 °C: 1.3

INDEX OF REFRACTION: 1.3715 AT 22 °C/D

UV: 3-22 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York) /Sec-butyl nitrite/

Coriolis coupling

Centrifugal distortion

Equilibrium structure

Molecular structure

Optical coefficient

Refractive index

Rotation-vibration spectrum

Rotational excitation cross section

Nitrogen Compounds -> Nitrates and Nitrites

Flammable agents - 3rd degree

Reactive agents - 4th degree

Highly flammable. Insoluble in water. Slowly decomposes in water.

Nitro, Nitroso, Nitrate, and Nitrite Compounds, Organic

Highly Flammable

An oxidizing agent but can serve as a reducing agent. May begin a vigorous reaction that culminates in a detonation if mixed with reducing agents, including hydrides, sulfides, nitrides, ammonium salts, cyanides, and many fuels.

Isobutyl nitrite

Group 2B: Possibly carcinogenic to humans

Volume 122: (2019) Isobutyl Nitrite, β-Picoline, and Some Acrylates

Isobutyl Nitrite

TR-448: Toxicology and Carcinogenesis Studies of Isobutyl Nitrite (CASRN 542-56-3) in F344/N Rats and B6C3F1 Mice (Inhalation Studies) (1996 )

11/29/94

Clear Evidence

Some Evidence

Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenic activity of isobutyl nitrite in male and female F344/N rats based on the increased incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined). There was some evidence of carcinogenic activity of isobutyl nitrite in male and female B6C3F1 mice based on the increased incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined) in males and females. The increased incidence of thyroid gland follicular cell adenoma in male mice may have been related to isobutyl nitrite exposure.

Exposure of rats and mice to isobutyl nitrite by inhalation for 2 years resulted in increased incidences of alveolar epithelial hyperplasia (male and female rats and mice), thyroid gland follicular cell hyperplasia and splenic hemosiderin pigmentation (male mice), and serous exudate and atrophy of the olfactory epithelium of the nose (female mice).

Exposure of rats to isobutyl nitrite by inhalation for 2 years resulted in decreased incidences of mononuclear cell leukemia in males and females.

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

Sore throat. Headache. Dizziness. Blue lips, fingernails and skin. Nausea. Confusion. Convulsions. Unconsciousness. Symptoms may be delayed.

See Inhalation.

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.

Methemoglobinemia - The presence of increased methemoglobin in the blood; the compound is classified as secondary toxic effect

IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.

ACGIH Carcinogen - Confirmed Animal.

LC50 (rat) = 777 ppm/4h

PRETREATMENT WITH A SINGLE DOSE OF METHYLENE BLUE PREVENTS THE METHEMOGLOBIN FORMATION AND PROTECTS AGAINST THE LETHALITY OF THE BUTYL NITRITES IN MICE.

THOUGH THE USUAL ROUTE OF ADMINISTRATION BY INHALATION HAS NOT RESULTED IN ANY TOXICOLOGICALLY VERIFIED DEATHS, ISOBUTYL NITRITE MAY CAUSE FATAL TOXIC METHEMOGLOBINEMIA IF INGESTED. A CASE WITH A FATAL OUTCOME IS PRESENTED.

METHEMOGLOBINEMIA OCCURRED IN A 36-YR-OLD MAN WHO INGESTED 15 ML OF ISOBUTYL NITRITE (RUSH). HE RECOVERED AFTER TREATMENT WITH INTRAVENOUS 1% METHYLENE BLUE, 20 ML, INFUSED OVER 20 MINUTES.

A CASE REPORT OF SEVERE AND PROLONGED TRACHEOBRONCHITIS IN A 23-YR-OLD MALE, FOLLOWING THE INHALATION OF 2 BOTTLES OF LOCKER ROOM (ISOBUTYL NITRITE), IS PRESENTED.

AT A 1% ADDED CONCN, ISOBUTYL NITRITE LYSED HUMAN LEUKOCYTES AND REDUCED VIABILITY FROM 95 TO 21% IN 24 HR. AT LESS THAN OR EQUAL TO 0.5%, CELL COUNT AND VIABILITY WERE UNAFFECTED, BUT ISOBUTYL NITRITE INHIBITED IN VITRO LYMPHOCYTE BLASTOGENIC RESPONSES TO PHYTOHEMAGGLUTININ, POKEWEED MITOGEN, AND CONCANAVALIN A. IT INHIBITED NATURAL KILLER CELL ACTIVITY TO THE K562 CELL LINE, LYMPHOCYTE-MEDIATED ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY TO THE CEM CELL LINE, MONOCYTE-MEDIATED ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY TO HUMAN RED BLOOD CELLS, AND IN VITRO ADHERENCE AND TRANSFORMATION OF MONOCYTES TO MACROPHAGES. INHIBITORY EFFECTS WERE GREATER THAN 90% AT 0.5% AND STILL DETECTABLE AT 0.01%. ISOBUTYL NITRITE INHIBITED LEUCINE, URIDINE, AND THYMIDINE INCORPORATION APPROX EQUALLY. AFTER 24 HR OF EXPOSURE, THE EFFECTS ON VARIOUS LYMPHOCYTE FUNCTION PARAMETERS WERE NOT REVERSIBLE.

IN DETERMINING LD50 VALUES (MICE, INTRAPERITONEAL) FOR EACH COMPOUND, NO DEATHS WERE OBSERVED AFTER 30 MINUTES POSTADMINISTRATION FOR ISOBUTYL NITRITE. GROSS POSTMORTEM EXAMINATION SUGGESTED THE DELAYED LETHALITY MAY BE DUE TO LIVER DAMAGE.

WHEN MICE WERE EXPOSED TO BUTYL NITRITES IN AN INHALATION CHAMBER, A SIGNIFICANT LEVEL OF METHEMOGLOBINEMIA IS PRODUCED. THE POTENCY ORDER FOR METHEMOGLOBIN PRODUCTION OF THE 4 BUTYL NITRITES N-BUTYL NITRITE, ISO-BUTYL NITRITE, SEC-BUTYL NITRITE, AND TERT-BUTYL NITRITE IS THE SAME AS THAT OF THEIR LC50 VALUES AND PARALLELS THE ABILITY OF THE AGENTS TO CAUSE METHEMOGLOBIN FORMATION IN MOUSE ERYTHROCYTES IN VITRO.

ORAL ADMIN OF SINGLE DOSES OF BUTYL NITRITES TO MICE YIELDED LD50 VALUES FROM 171 TO 428 MG/KG. THE LETHAL TOXICITY OF SINGLE DOSES OF ISOBUTYL NITRITE, THE ISOMER COMMONLY USED AS A RECREATIONAL DRUG, COULD BE REDUCED BY PRETREATMENT WITH METHYLENE BLUE OR TOLUIDINE BLUE.

WHEN TESTED BY THE AMES MUTAGENICITY TEST ON SALMONELLA, ISOBUTYL NITRITE WAS MUTAGENIC WITH OR WITHOUT METABOLIC ACTIVATION. THE POTENTIAL CARCINOGENIC RISK OF SOME ALIPHATIC NITRITES, WHICH ARE BEING USED AS STREET DRUGS, IS DISCUSSED.

For more Non-Human Toxicity Excerpts (Complete) data for ISOBUTYL NITRITE (8 total), please visit the HSDB record page.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=542-56-3]

... Male and female F344/N rats and B6C3F1 mice were exposed to isobutyl nitrite (purity of 93% or greater) by inhalation for ... 2 years. ... 2-YEAR STUDY IN RATS: ... Isobutyl nitrite exposure concentrations selected for the 2 yr inhalation study in rats were 37.5, 75, and 150 ppm. Groups of 56 male and 56 female rats were exposed to 0, 37.5, 75, or 150 ppm (equivalent to 0, 158, 315, or 630 mg/cu m) isobutyl nitrite by inhalation for 6 hr/ day, 5 days/wk, for 103 wk. ... 2 YEAR STUDY IN MICE: ... Isobutyl nitrite exposure concentrations selected for the 2 yr inhalation study in mice were 37.5, 75, and 150 ppm. Groups of 60 male and 60 female mice were exposed to 0, 37.5, 75, or 150 ppm (equivalent to 0, 158. 315, or 630 mg/cu m) isobutyl nitrite by inhalation for 6 hr/day, 5 days/wk, for 103 wk. ... CONCLUSIONS: Under the conditions of these 2 year inhalation studies, there was clear evidence of carcinogenic activity of isobutyl nitrite in male and female F344/N rats based on the increased incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined). There was some evidence of carcinogenic activity of isobutyl nitrite in male and female B6C3F1 mice based on the increased incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma (combined) in males andfemales. The increased incidence of thyroid gland follicular cell adenoma in male mice may have been related to isobutyl nitrite exposure.

Flammable Liquid Poison

Do not transport with food and feedstuffs.

Symbol: F, T; R: 11-20/22-45-68; S: 53-45; Note: E

UN Hazard Class: 3; UN Subsidiary Risks: 6.1; UN Pack Group: III