2,2,4-Trimethylpentane

Hazardous Air Pollutants (HAPs)

Flammable agents - 3rd degree

Cosmetic ingredients (Isooctane) -> CIR (Cosmetic Ingredient Review)

Solvent

0.69194 @ 20 °C/4 °C

Relative density (water = 1): 0.69

0.692 @ 20°C

MOBILE LIQUID

COLORLESS LIQUID

PRACTICALLY INSOL IN WATER; SOMEWHAT SOL IN ABS ALC; SOL IN BENZENE, TOLUENE, XYLENE, CHLOROFORM, ETHER, CARBON DISULFIDE, CARBON TETRACHLORIDE, DMF & OILS, EXCEPT CASTOR OIL.

MISCIBLE WITH ACETONE, HEPTANE.

Solubility in water: none

10 °F (NFPA, 2010)

-12 °C

4.5 °C (OPEN CUP)

4.5 °C o.c.

Danger

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

P210, P233, P240, P241, P242, P243, P261, P264, P271, P273, P280, P301+P316, P302+P352, P303+P361+P353, P304+P340, P319, P321, P331, P332+P317, P362+P364, P370+P378, P391, P403+P233, P403+P235, P405, and P501 (click each P-code to see the statement)

Danger

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

P210, P233, P240, P241, P242, P243, P261, P264, P271, P273, P280, P301+P316, P302+P352, P303+P361+P353, P304+P340, P319, P321, P331, P332+P317, P362+P364, P370+P378, P391, P403+P233, P403+P235, P405, and P501 (click each P-code to see the statement)

Chemical: Pentane, 2,2,4-trimethyl-

Hazard Traits - Neurotoxicity; Respiratory Toxicity

Pentane, 2,2,4-trimethyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Pentane, 2,2,4-trimethyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Isooctane is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Isooctane are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 11-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/13847

Status: Active Update: 01-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/26046

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]:

· HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames.

Highly flammable. Vapour/air mixtures are explosive.

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]:

CAUTION: Petroleum crude oil (UN1267) may contain TOXIC hydrogen sulphide gas.

2,2,4-Trimethylpentane is released to the environment through the manufacture, use, and disposal of products associated with the petroleum and gasoline industry. During an accident, 2,2,4-trimethylpentane penetrated the skin of a human which caused necrosis of the skin and tissue in the hand and required surgery. No other information is available on the acute (short-term) effects in humans. Irritation of the lungs, edema, and hemorrhage have been reported in rodents acutely exposed by inhalation and injection. No information is available on the chronic (long-term), reproductive, developmental, or carcinogenic effects of 2,2,4-trimethylpentane in humans. Kidney and liver effects have been observed in rats chronically exposed via gavage (experimentally placing the chemical in the stomach) and inhalation. EPA has not classified 2,2,4-trimethylpentane with respect to potential carcinogenicity.

A skin, eye, and respiratory tract irritant; May cause kidney and liver injury; Inhalation of high concentrations can cause CNS depression; [ICSC] An irritant; In high-dose animal studies, causes liver and kidney injury; [MSDSonline] See Octane.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Pentane, 2,2,4-trimethyl- is included on this list.

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]:

Use powder, AFFF, foam, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water. Combat fire from a sheltered position.

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

Remove contaminated clothes. Rinse and then wash skin with water and soap.

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

Rinse mouth. Do NOT induce vomiting. Refer for medical attention .

· 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.

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

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]:

General First Aid:

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

500.0 [ppm]

Evacuate danger area! Personal protection: self-contained breathing apparatus. 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.

Excerpt from ERG Guide 128 [Flammable Liquids (Water-Immiscible)]:

Immediate precautionary measure

NO open flames, NO sparks and NO smoking. Closed system, ventilation, explosion-proof electrical equipment and lighting. Prevent build-up of electrostatic charges (e.g., by grounding). Do NOT use compressed air for filling, discharging, or handling.

RABBITS WERE EXPOSED TO 2500 OR 5000 PPM CARBON MONOXIDE, WITH OR WITHOUT 5000 PPM OCTANE, OR ISO-OCTANE, OR TO AUTOMOBILE EXHAUST FUMES. THE HYDROCARBONS ENHANCED THE CARBON MONOXIDE INDUCED HYPOTENSION & BRADYCARDIA, BUT HASTENED THE RECOVERY FROM THE CARBON MONOXIDE INDUCED ELECTROCARDIOGRAPHIC MODIFICATIONS.

TERRESTRIAL FATE: Photolysis and hydrolysis of iso-octane are not expected to important in soil(2,6). Although iso-octane may undergo slow biodegradation in soil(5), volatilization from dry and wet soil surfaces is expected to be more important fate process. The vapor pressure of 49.3 mm Hg(3) and a value of 3.01 atm cu-m/mole for Henry's Law constant(4) indicates high volatility from dry and moist soil surface. In subsurface soil, adsorption of iso-octane is expected to be important as indicated by average log Koc value of 4.35 in three sediments(1) and an estimated log Koc value of 3.43 in soil(2).

AQUATIC FATE: The hydrolysis of iso-octane in water is not expected to be important because the compound does not contain any hydrolyzable group(2). The photolysis of the compound in water is also expected to be unimportant because iso-octane is transparent to wavelengths available in sunlight(5). Although slow biodegradation may occur in aquatic medium(4), volatilization from water is expected to be the dominant process as indicated by the value 3.01 atm-cu m/mole for Henry's law constant(3). The average log Koc value of 4.35 in sediments(1) indicate that most of the compound may remain adsorbed to sediment and suspended solids in aquatic medium. A log bioconcentration factor of 2.57 estimated from a regression equation based on water solubility(2) indicates that bioconcentration in aquatic organisms may be important.

ATMOSPHERIC FATE: The rate constant for the reaction of iso-octane with atomic oxygen (3P) is 5.5X10+10 cu cm/mol-sec(3). Based on this rate constant and the concentration of atomic oxygen of 2.5X10+4 molecules/cu cm in a typical atmosphere(4), this reaction may not be important in the atmosphere. The gas-phase reactions of alkanes with ozone and nitrate radicals are of negligible importance as atmospheric loss processes(1). The rate constant for the reaction of iso-octane with OH radicals at 25 °C is given as 3.66-3.68X10-12 cu cm/molecule-sec(1,2). Based on an average 24-hr atmospheric OH radical concentration of 5X10+5 molecules/cu cm(5), the half-live of iso-octane due to this reaction is 4.4 days.

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

Oral (L400) ; inhalation (L400) ; dermal (L400)

Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org

Petroleum distillates are central nervous system depressants and cause pulmonary damage. (A600)

Confusion. Dizziness. Headache. Nausea. Vomiting.

Dry skin. Redness. Pain.

Redness.

Further see Inhalation.

Petroleum distillate poisoning may cause nausea, vomiting, cough, pulmonary irritation progressing to pulmonary edema, bloody sputum, and bronchial pneumonia. At high amounts, central nervous system depression may also occur, with symptoms such as weakness, dizziness, slow and shallow respiration, unconsciousness, and convulsions. Petroleum distillates are also irritating to the skin. (A594)

The average exhaust from 67 gasoline fueled vehicles driven through an Australian urban driving cycle on a chassis dynamometer contained 1% (w/w) iso-octane of the total non-methane hydrocarbon emitted(3). The average emission of iso-octane from 46 in-use emission-controlled U.S. passenger cars made between 1975-1982 was 2.4% of the total emission (both exhaust and evaporative) under federal test procedure (FTP) driving cycle(2). On the average, 0.25% of the total non-methane hydrocarbon emitted from a wood combustion stack was due to iso-octane(4). Iso-octane has been detected in emitted gases from waste and landfill sites(1,5).

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Pentane, 2,2,4-trimethyl- is included on this list.

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Iso-octane is included on this list.

The mechanism by which 2,2,4-trimethylpentane related radiolabel was retained in the kidneys after dosing of Fischer 344 rats with 4.4 millimoles/kg radiolabeled 2,2,4-trimethylpentane was studied. The subcellular localization of radioactivity in the kidney was examined. The nature of the association of the parent compound or any metabolite with alpha2u-globulin in the kidney, liver, plasma and urine of male rats and in the kidney of female rats was investigated. More radiolabeled material was detected in the kidneys of male than female rats. Subcellular fractionation of male kidneys 24 hours after dosing with 2,2,4-trimethylpentane, by centrifugation at 116,000 times gravity, resulted in an association of 60% of the radiolebeled material with the supernatant. Two components were obtained from this supernatant by column chromatography. One component contained 26% of the radiolabel and coeluted with alpha2u-globulin and cross reacted with an antibody specific for this globulin. the other component, which the authors suggest contains 2,2,4-trimethylpentane metabolites, eluted in a low molecular weight range. Column chromatography analysis was performed of the male liver and female kidney 116,000 times gravity supernatants, and of male urine and plasma, 24 hr after administration of 2,2,4-trimethylpentane. Radiolabel from 2,2,4-trimethylpentane in male urine resolved into the same two components as the male kidney supernatant. Radiolabel in male liver and female kidney supernatants eluted as a single component with a low molecular weight. The metabolite bound to the male rat kidney fraction containing alpha2u-globulin was identified as 2,4,4-trimethyl-2-pentanol. The amount of this metabolite retained in the kidneys was maximal by 24 hr and then remained virtually constant for 72 hr.

Subchronic exposure of male rats to the nephrotoxin 2,2,4-trimethylpentane causes accumulation of protein droplets in the epithelial cells of the renal cortex. Experimental evidence suggests that these droplets contain alpha 2u-globulin, a low molecular weight protein found specifically in the urine of male rats. It has been proposed that aldehyde metabolites of 2,2,4-trimethylpentane form Schiff base adducts with the lysine groups of alpha 2u-globulin and thereby inhibit renal lysosomal processing of the protein. Accordingly, the ability of 2,2,4-trimethylpentane and its metabolites to covalently bind to alpha 2u-globulin was examined. As a model, a (14)C formaldehyde-alpha 2u-globulin Schiff base was formed. This protein adduct was stabilized by reduction with cyanoborohydride and could be identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that hepatocytes isolated from male Fischer 344 rats produced significant quantities of alpha 2u-globulin in culture, whereas hepatocytes from female rats did not. A 15 hr exposure of metabolically competent, primary cultures of male rat hepatocytes to (14)C 2,2,4-trimethylpentane (0.1 and 0.5%, v/v), followed by reduction with cyanoborohydride, dialysis, and analysis with sodium dodecyl sulfate polyacrylamide gel eletrophoresis, revealed no evidence of radiolabeled alpha 2u-globulin. Analysis as above showed no 2,2,4-trimethylpentane derived radioactivity in fractions containing alpha 2u-globulin from liver, blood, kidney cortex, or urine. The absence of a detectable covalent interaction between 2,2,4-trimethylpentane and alpha 2u-globulin following in vitro or in vivo exposure suggests that 2,2,4-trimethylpentane alpha 2u-globulin adduct is not responsible for the excessive formation of protein droplets in the renal cortex of exposed male rats.

Metabolism of 2,2,4-trimethylpentane probably occurs by omega and omega-l oxidation to yield the corresponding alcohol and acid metabolites. While the exact structure of these remains to be elucidated, there is evidence that the cytochrome p450 system, lauric acid hydroxylases, and palmitoyl CoA oxidase in the liver and kidneys play a role in the biotransformation of 2,2,4-trimethylpentane. Studies indicate that 2,2,4-trimethylpentane (radiolabeled with (14)C) is metabolized by the cytochrome p450 system and that modulation of this enzyme system (with phenobarbital and metyrapone) will alter the disposition and renal retention of 2,2,4-trimethylpentane. Pretreatment of male rats with phenobarbital decreased the expired organics (from 40 to 10% of dose) and increased the urine radioactivity (from 46 to 80%), but did not alter the retention of radioactivity in the kidneys. Metyrapone (an inhibitor of cytochrome p450) increased the elimination half-life of expired 2,2,4-trimethylpentane (2.8 to 3.8 hr), did not alter urinary radioactivity, and decreased radioactivity retention in the kidney by 37%. From these studies, elimination of 2,2,4-trimethylpentane (isooctane) occurs mainly by metabolism to water-soluble products which are excreted in the urine and by exhalation of parent material.

Metabolic disposition of 2,2,4-trimethylpentane was studied in male and female rats. Rats were treated with a single oral dose of (14)C 2,2,4-trimethylpentane (4.4 mmol/kg; 2 uCi/mmol). Identification and quantitation of the urinary metabolites of 2,2,4-trimethylpentane showed that both male and female rats metabolize 2,2,4-tremethylpentane via the same pathway and at a similar rate. Female rats, however, excreted more conjugates of 2,4,4-trimethyl-2-pentanol in urine than males. 2,4,4-Trimethyl-2-pentanol was the major metabolite present in the male rat kidney, but was absent in the female rat kidney.

When (14)C 2,2,4-trimethylpentane was administered to an adult male Fischer-344 rat (300 mg/kg, ig) 22, 16, and 10 hr before sacrifice, 16% of the administered radioactivity was eliminated in the urine as 2,2,4-trimethylpentane metabolites.

Volatile hydrocarbons are absorbed mainly through the lungs, and may also enter the body after ingestion via aspiration. (A600)

Respiration is the most likely route by which 2,2,4-trimethylpentane is absorbed. Although it has not been determined, the respiratory uptake of 2,2,4-trimethylpentane is probably similar to that seen for n-octane. Oral absorption of (14)C-2,2,4-trimethylpentane has been reported ... to occur to the extent of 86% in male rats based on recovery of radioactivity in urine, expired organics, and expired (14)C-carbon dioxide. Dermal bioavailability has not been reported, but absorption of 2,2,4-trimethylpentane through the skin would be expected to be minor based on percutaneous results reported for n-heptane and n-octane. Oral gavage studies ... in male rats with (14)C-2,2,4-trimethylpentane (0.5 mg/kg, single dose) revealed that the radioactivity is selectively distributed in the kidneys 72 hr after administration. It has been suggested that the renal retention of 2,2,4-trimethylpentane is related to the hydrocarbon-induced nephropathy observed specifically in male rats.

Metabolic disposition of 2,2,4-trimethylpentane was studied in male and female Fischer 334 rats. Rats were treated with a single oral dose of (14)C 2,2,4-trimethylpentane (4.4 mmol/kg; 2 microCi/mmol). Radiolabeled material in kidney, liver, and plasma was determined at 4, 8, 12, 24, and 48 hr after dosing. Maximum concentration of 2,2,4-trimethylpentane derived radioactivity in kidney, liver, and and plasma of male rats was found after 12 hr (1252, 1000, and 403 nmol eg/g, respectively), whereas those measured in females were found after 8 hr (557, 1163, and 317 nmol eq/g, respectively). A selective retention of the 2,2,4-trimethylpentane derived radiolabel in the kidneys of male rats was noted when peak tissue concentration was expressed as a percentage of administered dose. Kidney concentrations of 2,2,4-trimethylpentane derived radiolabel increased in a nonlinear, but dose dependent radiolabel increased in a nonlinear, but dose-dependent, manner; the kidney to plasma ratio was greater at low doses than at higher doses. Increased retention of radiolabel material in the kidney was associated with a significant increase in renal concentration of the male rat specific protein, alpha 2u-globulin, 24 and 48 hr after 2,2,4-trimethylpentane administration. Total radioactivity collected in urine 48 hr after 2,2,4-trimethylpentane administration was similar in males and females (32 and 31% of dose). Identification and quantitation of the urinary metabolites of 2,2,4-trimethylpentane showed that both male and female rats metabolize 2,2,4-trimethylpentane via the same pathway and at a similar rate. Female rats, however, excreted more conjugates of 2,4,4-trimethyl-2-pentanol in urine than males. 2,2,4-Trimethyl-2-pentanol was the major metabolite present in the male rat kidney, but was absent in the female rat kidney. The renal retention of 2,4,4-trimethyl-2-pentanol appears to account for the delayed clearance observed in the disposition of (14)C 2,2,4-trimethylpentane derived radiolabel. Based on the concomitant accumulations in renal alpha 2u-globulin concentration and renal 2,4,4-trimethyl-2-pentanol concentration, an association is speculated between these two components. The male rat specific accumulation of 2,4,4-trimethyl-2-pentanol may therefore reflect the accumulation of a metabolite-alpha 2u-globulin complex. This may be relevant to the male-rat-specific nephrotoxicity produced by 2,2,4-trimethyl-pentane.

A study was conducted to determine if the rate of uptake and route of excretion of inhaled hydrocarbons and their metabolites might be different for branched alkanes relative to straight chain isomers. Male F344/N rats were exposed by nose only inhalation to nominal concentrations of 1 or 350 ppm (14)C labeled octane and isooctane for a period of 2 hours. Urine and feces were collected as were exhalants at 3, 6, 9, 18, 24, 30, 42, 54, and 66 hr post exposure. Exhalants were also collected at 1 and 2 hr post exposure. Elimination was most exclusively via the kidneys for isooctane while octane was eliminated about equally in urine and as exhaled carbon dioxide. Isooctane was excreted through the kidneys over the entire 70 hr, whereas octane excretion was essentially completed after 10 to 20 hr. At 70 hr after exposure about 5% of the octane equivalents inhaled at 1 ppm remained in the carcass. The author suggests that the different patterns of metabolites excretion of isooctane compared to octane may be a factor affecting the differences in nephrotoxicity between these two compounds.

CIR ingredient: Isooctane

2,2,4-Trimethylpentane is used in determining octane numbers of fuels, in spectrophotometric analysis, as a solvent and thinner, and in organic syntheses.

Used in octane analysis of fuels and in spectrophotometric analysis; Also used as a solvent, thinner, and chemical intermediate; [HSDB]

Painting (Solvents) [Category: Paint]

IN DETERMINING OCTANE NUMBERS OF FUELS; IN SPECTROPHOTOMETRIC ANALYSIS; AS SOLVENT & THINNER.

IN ORG SYNTH

2023: 250,000,000 - <400,000,000 lb

2023: 57,000,000 lb

(1977) AT LEAST 4.99X10+8 GRAMS

(1982) PROBABLY GREATER THAN 2.27X10+6 GRAMS

CBI

Fuel

PRODUCED BY THE REFINING OF PETROLEUM

REACTION OF BUTYLENES WITH ISOBUTANE WITH SULFURIC ACID OR HYDROFLUORIC ACID CATALYST.

All Other Basic Organic Chemical Manufacturing

Petroleum Refineries

Pentane, 2,2,4-trimethyl-: ACTIVE

Isooctane: ACTIVE

The name isooctane has also been applied to 2-methylheptane.