Toluene 2,6-Diisocyanate

Carcinogens

Industrial compound

1.22 at 77 °F for a 80% 2,4:20% 2,6 TDI mixture (EPA, 1998) - Denser than water; will sink

1.22

1.2244 at 68 °F

Reaction (NTP, 1992)

Decomposes in water

Soluble in acetone, benzene

264 to 271 °F at 18 mmHg (EPA, 1998)

BP: 129-133 °C at 18 mm Hg

Specific gravity: 1.22 at 25 °C; BP: 250 °C; FP: 11.3-13.5 °C /80% 2,4:20% 2,6/

264-271 °F

68 to 72 °F for a 80% 2,4:20% 2,6 TDI mixture (EPA, 1998)

18.3 °C

68-72 °F

Danger

H315: Causes skin irritation [Warning Skin corrosion/irritation]

P203, P233, P260, P261, P264, P264+P265, P271, P272, P273, P280, P284, P302+P352, P304+P340, P305+P351+P338, P316, P318, P319, P320, P321, P332+P317, P333+P317, P337+P317, P342+P316, P362+P364, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 0.5% (6 of 1096) of reports.

Danger

H315 (99.5%): Causes skin irritation [Warning Skin corrosion/irritation]

Chemical: Benzene, 1,3-diisocyanato-2-methyl-

Benzene, 1,3-diisocyanato-2-methyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzene, 1,3-diisocyanato-2-methyl- 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)

SP - indicates a substance that is identified in a proposed Significant New Use Rule.

Status: Active Update: 31-03-2017 https://echa.europa.eu/registration-dossier/-/registered-dossier/18739

Restricted substance: 2-methyl-m-phenylene diisocyanate

Benzene, 1,3-diisocyanato-2-methyl-: Does not have an individual approval but may be used under an appropriate group standard

Classified as slightly toxic orally. Probable oral lethal dose in humans is 5 to 15 g/kg or between 1 pint and 1 quart for a 70 (l50 lb.) person. Particularly poisonous when breathed. This is among the most poisonous of isocyanates. Acute and chronic exposures to low concentrations may produce asthmatic attacks. (EPA, 1998)

U.S. Department of Health & Human Services/National Toxicology Program; Twelfth Report on Carcinogens (2011). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Toluene diisocyanates (26471-62-5) was first listed in the Fourth Annual Report on Carcinogens (1985) as reasonably anticipated to be a human carcinogen.[Available from, as of August 15, 2012: http://ntp.niehs.nih.gov/]

DHHS/NTP; Toxicology & Carcinogenesis Studies of Commercial Grade 2,4 (80%)- and 2,6 (20%)-Toluene Diisocyanate in F344/N Rats and B6C3F1 Mice(Gavage Studies) Technical Report Series No. 251 (1986) NIH Publication No. 86-2507

U223; As stipulated in 40 CFR 261.33, when toluene diisocyanate, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

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. Benzene, 1,3-diisocyanato-2-methyl- is included on this list. Effective date: 6/1/87; Sunset date: 12/19/95.

Should wear a self-contained breathing apparatus. Move container from fire area if you can do so without risk. Spray cooling water on containers that are exposed to flames until well after fire is out. Fight fire from maximum distance. Dike fire control water for later disposal; do not scatter the material.

Biological Exposure Indices (BEI) [ACGIH] - Toluene diamine in urine (with hydrolysis) = 5 ug/g creatine at end of shift; [TLVs and BEIs]

0.001 [ppm]

If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, dry chemical, or carbon dioxide. Use water spray to knock-down vapors. /Toluene diisocyanate/

Where there is a fire involving isocyanates, carbon dioxide or powder extinguishers must be employed. Firemen must be equipped with self-contained breathing apparatus. /Isocyanates/

Storage temp: 75-100 °F

Isocyanates are transported in railroad tank cars, tank trucks, tanks in ships, containers, and drums. They are stored in steel tanks and processed in steel equipment. For long-term storage stainless steel is recommended. To avoid contamination by atmospheric moisture, a dry air or inert gas blanket is essential. /Isocyanates/

SPILLED ISOCYANATES SHOULD BE DECONTAMINATED WITH SUITABLE SOLN, SUCH AS 10% AMMONIA WITH ALCOHOL. /ISOCYANATES/

AQUEOUS SOLUTIONS CONTAINING 10-20% (WT) OF A NONIONIC SURFACTANT, ARKOPAL-N100, WAS A USEFUL DECONTAMINATING AGENT FOR TOLYLENE DIISOCYANATE (TDI). THE SOLUTION CAN BE SPRAYED DIRECTLY ON SPILLS AS A LIQUID OR MAY BE APPLIED IN THE FORM OF A FOAM WHICH CAN BE GENERATED IN SUITABLE FIRE EXTINGUISHING EQUIPMENT. SOLID DECONTAMINANT FORMULATIONS WERE ALSO DEVELOPED WHICH CAN BE USED FOR GROUND SPILLS OF TDI.

Decontamination of spilled isocyanates and disposal of isocyanate waste are best conducted by using aqueous ammonia (3-8% concentrated ammonia solution in 90-95% water with 0.2-5% liquid detergent) or aqueous sodium carbonate (5-10% sodium carbonate in 90-95% water and 0.2-5% liquid detergent). An alcoholic solution (50% ethanol, isopropyl alcohol, or butanol; 45% water; and 5% concentrated ammonia) may be preferred because of the low miscibility of isocyanates with water. /Isocyanates/

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U223, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

Industrial waste must not be destroyed by burning. /Isocyanates/

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

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. Attempt to stop leak if without undue personnel hazard. Use water spray to knock-down vapors. /Toluene diisocyanate/

For more Preventive Measures (Complete) data for 2,6-TOLUENE DIISOCYANATE (14 total), please visit the HSDB record page.

0.001 [ppm], inhalable fraction and vapor

0.005 [ppm], inhalable fraction and vapor

8 hr Time Weighted Avg (TWA): 0.005 ppm; 15 min Short Term Exposure Limit (STEL): 0.02 ppm, sentizer. /Toluene-2,4- or 2,6-diisocyanate (or as a mixture)/

A4: Not classifiable as a human carcinogen. /Toluene-2,4- or 2,6-diisocyanate (or as a mixture)/

2011 Notice of Intended Changes: These substances, with their corresponding values and notations, comprise those for which (1) a limit is proposed for the first time, (2) a change in the Adopted value is proposed, (3) retention as an NIC is proposed, or (4) withdrawal of the Documentation and adopted TLV is proposed. In each case, the proposals should be considered trial values during the period they are on the NIC. These proposals were ratified by the ACGIH Board of Directors and will remain on the NIC for approximately one year following this ratification. If the Committee neither finds nor receives any substantive data that changes its scientific opinion regarding an NIC TLV, the Committee may then approve its recommendation to the ACGIH Board of Directors for adoption. If the Committee finds or receives substantive data that change its scientific opinion regarding an NIC TLV, the Committee may change its recommendation to the ACGIH Board of Directors for the matter to be either retained on or withdrawn from the NIC. Substance: Toluene-2,4- or 2,6-diisocyanate; Time Weighted Avg (TWA): 0.001 ppm (Inhalable fraction and vapor); Short Term Exposure Limit (STEL): 0.003 ppm (Inhalable fraction and vapor); Notations: Skin; A4: Not classifiable as a human carcinogen; sensitizer; Molecular Weight: 174.15; TLV Basis: asthma. /Toluene-2,4- or 2,6-diisocyanate (or as a mixture)/

0.001 ppm (inhalable fraction and vapor) [2015]

0.020 [ppm]

0.083 [ppm]

0.51 [ppm]

Antidotes to cyanide poisoning include hydroxocobalamin and sodium nitrite, which release the cyanide from the cytochrome system, and rhodanase, which is an enzyme occurring naturally in mammals that combines serum cyanide with thiosulfate, producing comparatively harmless thiocyanate. Oxygen therapy can also be administered. (L97)

Exposure to high levels of cyanide for a short time harms the brain and heart and can even cause coma, seizures, apnea, cardiac arrest and death. Chronic inhalation of cyanide causes breathing difficulties, chest pain, vomiting, blood changes, headaches, and enlargement of the thyroid gland. Skin contact with cyanide salts can irritate and produce sores. (L96, L97)

LC50; Species: Pimephales promelas (fathead minnow); Concentration: 195 mg/L for 24 hr; 172 mg/L for 48 hr; 164 mg/L for 96 hr /Conditions of bioassay not specified/

LD50; Species: Agelaius phoeniceus oral 100 mg/kg

LD50; Species: Sturnus vulgaris oral >100 mg/kg

No observed lethal concentration: Palaemonetes pugia (grass shrimp) < 508 mg/L /Conditions of bioassay not specified/

TERRESTRIAL FATE: 2,6-Toluene diisocyanate reacts readily with water(1); therefore, hydrolysis will be the dominant fate process in moist soil and leaching of 2,6-toluene diisocyanate in soil should not be important(SRC). There is no environmental fate data on the isolated 2,6-toluene diisocyanate. Ten days after a spill of 13 tons of toluene diisocyanate (TDI) (2,4- plus 2,6-isomers) onto a swampy, wet forest soil, TDI and toluenediamines were found in the soil(2,3). The TDI solidified and the area was covered with sand. The soil concentration of TDI and toluenediamine combined declined from the parts per thousand to parts per million range between 10 days and 12 weeks after the spill(3). One year later, neither TDI nor toluenediamine could be found in soil samples(4). After 6 years, only TDI-derived polyureas were found at the site in soil samples at depths to 100 cm(4). In a simulated spill, 5 kg of TDI in a container was covered with 50 kg of sand and 5 kg of water at ambient temperatures and samples were taken from the top and bottom of the sand pile(3); after 24 hours, 5.5% of the TDI remained unreacted and after 8 days 3.5% remained(3); the reaction product was largely polyureas(3).

AQUATIC FATE: 2,6-Toluene diisocyanate is not likely to be found in waste water streams because of its reactivity with water(1), therefore adsorption to suspended solids and sediment is not expected. Since 2,6-toluene diisocyanate hydrolyzes rapidly(1), bioconcentration is not likely to occur(SRC). Based upon data for the mixture, 2,6-toluene diisocyanate may not be persistent in the environment(SRC). When low concentrations of TDI (2,4- plus 2,6-isomers) are released into model river or seaway systems, it is hydrolyzed within a day(3). In order to simulate a spill of TDI in stagnant water, 0.5 liters of TDI was poured into 20 liters of water at pH 5, 7, or 9 at 20 °C. A hard compact crust formed at the water-TDI interface(2). This crust thickened over a period of 30 days until no liquid TDI remained. The solid crust contained <0.5% of the original TDI after 35 days(2). Another experiment was performed to simulate a spill into running water by pouring 0.5 liters of TDI into 20 liters of slowly overflowing water. Trace amounts of toluenediamine were present in the overflow samples. As in the stagnant water simulation, a crust formed that contained <0.5% of the original TDI after 35 days(2).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2,6-toluene diisocyanate, which has a vapor pressure of 2.09X10-2 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 2,6-toluene diisocyanate 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 20 hrs(SRC), calculated from its rate constant of 6.3X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). However, 2,6-toluene diisocyanate decomposes in water(4); therefore, atmospheric degradation may also occur through contact with clouds, fog or rain(SRC). 2,6-Toluene diisocyanate does not contain chromophores that absorb at wavelengths >290 nm(5) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)

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.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=91-08-7]

The assessment of toluene diisocyanate exposure can be accomplished through measurement of the isomer-specific metabolites, 2,4-toluene diamine and 2,6-toluene diamine. This test may be useful for identification of exposures from both inhalation and dermal absorption. However, collection of urine samples must be obtained shortly after exposure, since later samples correlated poorly with exposure. Serum or Plasma Reference Ranges: Normal - not established; Exposed - not established; Toxic - not established. Urine Reference Ranges: Normal - none detected; Exposed - exposure to air level of 40 ug/cu m (current TLV) gave a 6 to 8 hour urine level of 8.6 ug/l (average); Toxic - not established. /Toluene diisocyanate/

Respiratory Symptoms Questionnaires: Questionnaires published by the American Thoracic Society (ATS) and the British Medical Research Council have proven useful for identifying people with chronic bronchitis. Certain pulmonary function tests such as the FEV1 ... have been found to be better predictors of chronic airflow obstruction. /Toluene diisocyanate/

Chest Radiography: Chest radiographs are widely used to assess pulmonary disease. They are useful for detecting early lung cancer in asymptomatic people, and especially for detecting peripheral tumors such as adenocarcinomas. However, even though OSHA mandates this test for exposure to some toxicants such as asbestos, experts' views on the risk-to-benefit ratio in detection of pulmonary disease conflict, so routine annual chest x-rays are not recommended for all people. /Toluene diisocyanate/

Pulmonary Function Tests: The tests that have been found to be practical for population monitoring include: Spirometry and expiratory flow volume curves; Determination of lung volumes; Diffusing capacity for carbon monoxide; Single breath nitrogen washout; Inhalation challenge tests; Serial measurements of peak expiratory flow; Exercise testing; Spirometry, for the measurement of FVC(forced vital capacity) and FEV1 (forced expiratory volume in 1 second), has been found to be the most reproducible and least variable test of pulmonary function. /Toluene diisocyanate/

U223; As stipulated in 40 CFR 261.33, when toluene diisocyanate, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

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. Benzene, 1,3-diisocyanato-2-methyl- is included on this list. Effective date: 6/1/87; Sunset date: 12/19/95.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Toluene 2,6-diisocyanate is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 100 lbs.

The apparent half-life of 2,6-TDI was dependent on the vehicle in which it was admin, its concn in the solvent, & the rate of mixing as the compound was added. In an aqueous suspension of stomach contents, the half-life of 2,6-TDI was <2 min, whereas in serum, the half-life was <30 sec.

Toluene diisocyanates (TDI) are commonly used in polyurethane (PU)-related products. TDIs have been documented as the leading cause of occupational asthma. Skin exposure to TDI in the workplace is common. However, no studies in the literature have investigated the exact biomarker concentration profile for skin TDI absorption through any in vivo animal studies. In this study a rat model was used to evaluate the TDI skin absorption to explore the dose-response pattern and to determine the kinetic characteristics of urinary toluene diamine (U-TDA) during skin exposure. TDIs were topically exposed on the dorsum of rat skin at 0.2%, 1% and 5%. Consecutive urine samples were collected for 6 days and U-TDA were analysed using GC/ECD. It was demonstrated in this rat study that absorption of 2,4- and 2,6-TDI through skin contact is possible. A clear dose-dependent skin absorption relationship for 2,4- and 2,6-TDI was demonstrated by the AUC, Cmax findings and accumulative amounts (r > or = 0.968). U-TDA concentration profiles in 6-day consecutive urine samples fit well in the first-order kinetics, although higher order kinetics could not be excluded for the high dose. The apparent half-lives for excretory urinary TDA were about 20 hr consistent at various skin exposures. It is concluded that skin absorption of TDI was confirmed in a rat model and a clear dose-dependent skin absorption relationship for 2,4- and 2,6-TDI was demonstrated. Excretory U-TDA concentrations in 6-day consecutive urine samples via skin exposure reveal the first-order kinetics and the half-lives were about 20 hr.

The toxicokinetics of 2,4- and 2,6-toluenediisocyanates in 11 chronically exposed workers at two flexible foam polyurethane production plants have been reported. ... The half life in urine ranged from 5.8 to 11 days for 2,4 and 2.6 toluene diamines. The differences in exposure were reflected by the plasma toluene diamine concentrations. The mean half life in plasma was 21 (range, 14-34) days for 2,4-toluene diamine and 21 (16-26) days for 2,6-toluene diamine. The study showed that the half life in plasma of chronically exposed workers for 2,4- and 2,6-toluene diamine was twice as long as for volunteers with short term exposure.

Two men were exposed to toluene diisocyanate atmospheres at three different air concn (ca 25, 50 & 70 ug/cu m). The toluene diisocyanate atmospheres were generated by a gas-phase permeation method, & the exposures were performed in an 8-cu m stainless-steel test chamber. ... The isomeric composition of the air in the test chamber was 30% 2,4-toluene diisocyanate and 70% 2,6-toluene diisocyanate. ... In plasma, 2,4- & 2,6-toluenediamine showed a rapid-phase elimination half-time of ca 2-5 hr, & that for the slow phase was greater than 6 days. ... The cumulated amount of 2,4-toluenediamine excreted in the urine over 24 hr was ca 15%-19% of the estimated inhaled dose of 2,4-toluene diisocyanate, & that of 2,6-toluenediamine was ca 17%-23% of the inhaled dose of 2,6-toluene diisocyanate.

Subjects exposed to 2,4-TDI and 2,6-TDI in a test chamber (5.5 ppb for 7.5 hours) had the corresponding amines in plasma and urine - identified by gas chromatography-mass spectrometry (GC-MS) after hydrolysis. Elimination from plasma was slow. Elimination in urine had a slow and a fast phase, the latter with a biological half time of one to two hours. Two persons were exposed to three concentrations in the range 3.4-9.7 ppb for 4 hours, and there was a correlation between TDI levels in air and TDA levels in plasma. Elimination from plasma had two phases. The biological half time was two to five hours for the fast phase and more than six days for the slow phase.

Cyanide is rapidly alsorbed through oral, inhalation, and dermal routes and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)

/(14)C-2, 6-toluene diisocyanate (TDI)/ urinary excretion /was/ 5 % at 900 mg/kg ... /and/ 12 % at 60 mg/kg. Half /of (14)C /at 60 mg/kg /consisted of/ 2,6-bis(acetylamino)toluene. 14C-fecal excretion /was/ 20-50 % at 900 mg/kg, 55-65 % at 60 mg/kg. 14C-tissue concentrations /were/ highest in blood, liver, kidney and stomach at 900 mg/kg and in blood and kidney at 60 mg/kg... /The study suggests/ that at lower doses 2, 6-TDI /are/ hydrolyzed in stomach then absorbed and acetylated prior to urinary excretion.

Most 2,6-TDI derived materials were excreted in feces or were found in the GI tract 72 hrs after dosing. Excretion in breath was insignificant. Approx 2.5 times as much 2,6-TDI derived materials were excreted in urine after a 60 mg/kg oral dose (12%) than after a 900 mg/kg dose (5%). More than half of the xenobiotic related material excreted in urine was 2,6-bis(acetylamino)toluene. Increased urinary excretion of metabolites of 2,6-TDI with decreasing dosage is consistent with the lower concn of 2,6-TDI in the stomach permitting increasing amounts of the 2,6-TDI to be hydrolyzed completely to monomeric 2,6-diaminotoluene rather than forming polymers. The 2,6-diaminotoluene could then be absorbed, acetylated, & excreted in urine. 2,6-TDI derived materials were not concentrated in any tissues.

When (14)C-2,6-TDI was given orally to rats in corn oil, most of the compound formed polymers in the GI tract. At doses of 900 mg/kg bw, the insoluble polyureas usually lined the stomach, slowing down or preventing the migration of stomach contents into the intestine. At a 60 mg/kg dose level, these results were not observed. Most 2,6-TDI-derived materials were eliminated in the feces or were found in the GI tract 72 hr after dosing. Approx 12% of the low dose (60 mg/kg bw) and only 5% of the high dose (900 mg/kg bw) were excreted in the urine (24 hr after treatment). Increased urinary excretion of 2,6-TDI metabolites with decreasing dosage was consistent with the lower concentration of the compound in the stomach permitting increasing amounts of the 2,6-TDI to be hydrolyzed completely to monomeric 2,6-diaminotoluene rather than forming polymers. The 2,6-diaminotoluene could than be absorbed, acetylated, and excreted in the urine. Materials derived from 2,6-TDI were not concentrated in any tissue.

The toxicokinetics of 2,4- and 2,6-toluenediisocyanates in 11 chronically exposed workers at two flexible foam polyurethane production plants have been reported. The toluene diisocyanate, concentrations in air varied between 0.4 and 4 ug/cu m in one plant and in the other between 10 and 120 ug/cu m. In one of the plants, the plasma 2,4-toluene diamine levels were 0.4-1 ug/mL before a 4-5 week holiday and 0.2-0.5 ug/mL afterwards. The corresponding plasma levels of 2,6-toluene diamine were 2-6 and 0.5-2 ug/mL, respectively. In the other plant, the plasma 2,4 toluene diamine concentrations were 2-23 ng/mL before the holiday and 0.5-6 ng/mL afterwards and those of 2,6-toluene diamine were 7-24 ng/mL before and 3-6 ng/mL afterwards. The plasma concentrations of 2,4-toluene diamine were, 2-24 ng/mL before a 12 day holiday, and 1-14 ng/mL afterwards. The corresponding values for plasma 2,6-toluene diamine were 12-29 and 8-17 ng/mL, respectively. The urinary elimination rates for 2,4-toluene diamine before the, holiday were 0.04-0.54 and 0.02-0.18 ug/hr afterwards. The corresponding values for 2,6-toluene diamine were 0.18-0.76 ug/hr before and 0.09-0.27 ug/hr after the holiday. The half life in urine ranged from 5.8 to 11 days for 2,4 and 2,6 toluene diamines. The differences in exposure were reflected by the plasma toluene diamine concentrations. The mean half life in plasma was 21 (range, 14-34) days for 2,4-toluene diamine and 21 (16-26) days for 2,6-toluene diamine, The study showed that the half life in plasma of chronically exposed workers for 2,4- and 2,6-toluene diamine was twice as long as for volunteers with short term exposure. An indication of a two phase elimination pattern in urine was found. The first phase was related to the more recent exposure and the second, much slower one was probably related to release of toluene diamines in urine from toluene diisocyanate adducts in the body.

Two men were exposed to toluene diisocyanate atmospheres at 3 different air concentrations (ca 25, 50 & 70 ug/cu m). The toluene diisocyanate atmospheres were generated by a gas-phase permeation method, & the exposures were performed in an 8-cu m stainless-steel test chamber. The effective exposure period was 4 hr. The isomeric composition of the air in the test chamber was 30% 2,4-toluene diisocyanate & 70% 2,6-toluene diisocyanate. The concentration of toluene diisocyanate in air of the test chamber was determined by an HPLC method using the 9-(N-methyl-amino-methyl)-anthracene reagent & by a continuous-monitoring filter-tape instrument. Following the hydrolysis of plasma & urine, the related amines, 2,4-toluenediamine & 2,6-toluenediamine, were determined as pentafluoropropionic anhydride derivatives by capillary gas chromatography using selected ion monitoring in the electron impact mode. In plasma, 2,4- & 2,6-toluenediamine showed a rapid-phase elimination half-time of ca 2-5 hr, & that for the slow phase was >6 days. A connection was observed between concn of 2,4- & 2,6-toluene diisocyanate in air & the levels of 2,4- & 2,6-toluenediamine in plasma. The cumulated amount of 2,4-toluenediamine excreted in the urine over 24 hr was ca 15%-19% of the estimated inhaled dose of 2,4-toluene diisocyanate, & that of 2,6-toluenediamine was ca 17%-23% of the inhaled dose of 2,6-toluene diisocyanate. A connection was found between the cumulated (24 hr) urinary excretion of 2,4- & 2,6-toluenediamine & the air concentratio of 2,4- & 2,6-toluene diisocyanate in the test chamber.

Occupational asthma reported in floor varnishers and in workers manufacturing polyurethane foams and elastomers; [Malo]

Painting (Pigments, Binders, and Biocides) [Category: Paint]

In the preparation of polyurethane foams, elastomers and coatings, as a cross-linking agent for nylon-6, and as a hardener in polyurethane adhesives and finishes. /2,4/2,6-Toluene diisocyanate (mixed)/

CHEMICAL INTERMEDIATE

(1983) 2.00X10+9 G /FOR 2,4 (AND 2,6) TDI/

(1983) 8.94X10+8 G /FOR TDI (UNMIXED)/

2023: 50,000,000 - <100,000,000 lb

(1984) 6.00X10+10 G (EST FOR 2,6 ISOMER) /BASED ON VALUE GIVEN FOR 80:20 MIX OF 2,4-2,6 ISOMER/

Benzene, 1,3-diisocyanato-2-methyl- is listed as a High Production Volume (HPV) chemical (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#5329]

Production volume for non-confidential chemicals reported under the 2006 Inventory Update Rule. Chemical: Benzene, 1,3-diisocyanato-2-methyl-. Aggregated National Production Volume: < 500,000 pounds.

... (80% 2,4-isomer and 20% 2,6-isomer) is produced commercially by nitrating toluene with nitric acid-sulfuric acid mixture and catalytically reducing resultant dinitrotoluene ... to toluenediamine mixture. ... This is dissolved in monochlorobenzene or ortho-dichlorobenzene and treated with phosgene. ... /Mixture of 2,4- & 2,6-isomers/

Toluene is the primary raw material for industrial TDI manufacture. The classical dinitration of toluene with mixed acid produces a mixture of 2,4- and 2,6-dinitro isomers in a ratio of 80:20. Catalytic reduction of these derivatives under hydrogen pressure leads to the corresponding diamines TDA, which are subsequently treated with phosgene to give TDI.

Commonly used isomers are 2,4-toluene diisocyanate and 2,6-toluene diisocyanate, commercially avail in following 3 ratios: 1) 100% 2,4-; 2) 80% 2,4-: 20% 2,6-; 3) 65% 2,4-: 35% 2,6-; 80% 2,4-: 20% 2,6 mixture represents over 95% of industrial usage ... .

Purity grade above 97%

Miscellaneous Manufacturing

Benzene, 1,3-diisocyanato-2-methyl-: ACTIVE

Commercial toluene diisocyanate (TDI) typically contains 20% of 2,6-toluene diisocyanate.