More About Toluene And Outgassing Of Pillows

Reports from studies on toluene exposure to animals

by IARC, HSDB, and RTECS

I got chastised by a member by referring to Toluene as carcinogenic. Here is my reply and source material for my remarks. You be the judge. The fact is the EPA has not classified Toluene as carcinogenic for HUMANS - YET.

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I replied:
"You are right- it has not been classified by the EPA as carcinogenic for humans. But it certainly is not good for your health which was the point of what I was trying to get across. I will correct in the next newsletter. The EPA has not classified this as a carcinogenic substance for humans although there is some fairly compelling data suggesting carcinogenic effects in laboratory animals.

See below:

"Health Effects
A serious health concern is that toluene may have an effect on your brain. Toluene can cause headaches, confusion, and memory loss. Whether or not toluene does this to you depends on the amount you take in and how long you are exposed. Low to moderate, day-after-day exposure in your workplace can cause tiredness, confusion, weakness, drunken-type actions, memory loss, nausea, and loss of appetite. These symptoms usually disappear when exposure is stopped. Researchers do not know if the low levels of toluene you breathe at work will cause any permanent effects on your brain or body after many years. You may experience some hearing loss after long-term daily exposure to toluene in the workplace.

If you are exposed to a large amount of toluene in a short time because you deliberately sniff paint or glue, you will first feel light-headed. If exposure continues, you can become dizzy, sleepy, or unconscious. You might even die. Toluene causes death by interfering with the way you breathe and the way your heart beats. When exposure is stopped, the sleepiness and dizziness will go away and you will feel normal again.

If you choose to repeatedly breathe in toluene from glue or paint thinners, you may permanently damage your brain. You may also experience problems with your speech, vision, or hearing, have loss of muscle control, loss of memory, poor balance, and decreased mental ability. Some of these changes may be permanent.

Toluene may change the way your kidneys work, but in most cases, the kidneys will return to normal after exposure stops. If you drink alcohol and are exposed to toluene, the combination can affect your liver more than either compound alone. This phenomenon is called synergism. Combinations of toluene and some common medicines like aspirin and acetaminophen may increase the effects of toluene on your hearing.

In animals, the main effect of toluene is on the nervous system. Animals exposed to moderate or high levels of toluene may also show slightly adverse effects in their liver, kidneys, and lungs.

Several studies have shown that unborn animals were harmed when high levels of toluene were breathed in by their mothers. When the mothers were fed high levels of toluene, the unborn animals did not show any structural birth defects, although some effects on behavior were noted. We do not know if toluene would harm your unborn child if you drink water or breathe air containing low levels of toluene, because studies in people are not comprehensive enough to measure this effect. However, if you deliberately breathe in large amounts of toluene during your pregnancy, your baby can have neurological problems and retarded growth and development.

Studies in workers and in animals exposed to toluene indicate that toluene does not cause cancer. The International Agency for Research on Cancer (IARC) and the Department of Health and Human Services (DHHS) have not classified toluene for carcinogenic effects. The EPA has determined that toluene is not classifiable as to its human carcinogenicity."

TOLUENE 2,4-DIISOCYANATE
584-84-9

Hazard Summary
CAUTION: Unless otherwise noted, the quantitative information on these fact sheets are from "EPA Health Effects Notebook for Hazardous Air Pollutants-Draft", EPA-452/D-95-00, PB95-503579, December 1994." Please conduct a current literature search and check the appropriate current online database for the most recent quantitative information.

Toluene 2,4-diisocyanate is extremely toxic from acute (short-term) and chronic (long-term) exposures. Acute exposure to high levels of toluene 2,4-diisocyanate in humans, via inhalation, results in severe irritation of the skin and eyes and affects the respiratory, gastrointestinal, and central nervous systems.

Chronic inhalation exposure to toluene 2,4-diisocyanate in humans has resulted in significant decreases in lung fuction in workers, an asthma-like reaction characterized by wheezing, dyspnea, and bronchial constriction, and effects on the liver, blood, and kidneys.

The Reference Concentration (RfC) for toluene 2,4-diisocyanate is under review by the U.S. Environmental Protection Agency (EPA).

EPA has not established a Reference Dose (RfD) for toluene 2,4-diisocyanate.
No information is available on the reproductive or developmental effects of toluene 2,4-diisocyanate in humans or animals.

No information is available on the carcinogenic effects of toluene 2,4-diisocyanate in humans. Animal studies have reported significantly increased incidences of tumors of the pancreas, liver, and mammary glands from exposure to toluene 2,4-diisocyanate via gavage (experimentally placing the chemical in the stomach). Animal studies, via inhalation, did not report an increased tumor incidence. EPA has not classified toluene 2,4-diisocyanate for carcinogenicity. The International Agency for Research on Cancer (IARC) has classified toluene 2,4-diisocyanate as a Group 2B, possible human carcinogen.

Please Note: The main sources of information for this fact sheet are the International Agency for Research on Cancer's (IARC's) Monograph on the Evaluation of the Carcinogenic Risk of Toluene 2,4-Diisocyanate to Humans, the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature, and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure
Occupational exposure to toluene 2,4-diisocyanate can occur for those workers involved in its manufacture and use. (1)

The general public may be exposed to toluene 2,4-diisocyanate through the use of several commercially available household products, including polyurethane foam kits. (1)
Toluene 2,4-diisocyanate may also be present in indoor air, due to its possible presence as an unreacted monomer in polyurethane. (1)

Assessing Personal Exposure
No information is available on the assessment of personal exposure to toluene 2,4-diisocyanate.

Health Hazard Information
Acute Effects:
Acute (short-term) exposure to high levels of toluene 2,4-diisoycanate in humans, via inhalation, results in severe irritation of the skin, eyes, and nose and affects the gastrointestinal and central nervous systems. (2,3)
Acute animal tests, such as the LC50 and LD50 test in rats, have shown toluene 2,4-diisocyanate to have moderate to extreme acute toxicity from inhalation exposure and low acute toxicity from oral exposure. (1,4)
EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, considers 2,4-diisoycanate to be a "high concern" pollutant based on severe acute toxicity. (5)

Chronic Effects (Noncancer):
Chronic (long-term) inhalation exposure to toluene 2,4-diisocyanate in workers has caused significant decreases in lung function, an asthma-like reaction characterized by wheezing, dyspnea, and bronchial constriction, and effects on the liver, blood, and kidneys. (2,3)
Animal studies have reported bronchopneumonia, weight loss, and effects on the liver from chronic exposure to toluene 2,4-diisocyanate. (1,2)
The RfC for toluene 2,4-diisocyanate is under review by EPA. (3)
EPA has not established an RfD for toluene 2,4-diisocyanate. (3)

Reproductive/Developmental Effects:
No information is available on the reproductive or developmental effects of toluene 2,4-diisocyanate in humans or animals.

Cancer Risk:
No information is available on the carcinogenic effects of toluene 2,4-diisocyanate in humans.

Animal studies have reported significantly increased incidences of tumors of the pancreas, liver, and mammary glands from exposure to toluene 2,4-diisocyanate via gavage. Animal studies, via inhalation, did not report an increased incidence of tumors. (1,6)

EPA has not classified toluene 2,4-diisocyanate for carcinogenicity. (3)

IARC has classified toluene 2,4-diisocyanate as a Group 2B, possible human carcinogen. (6)

Physical Properties
Toluene 2,4-diisocyanate is a colorless, yellow, or dark liquid with a sweet, fruity, pungent odor. (7)

The odor threshod for toluene 2,4-diisocyanate is 0.17 ppm. (8)

The chemical formula for toluene 2,4-diisocyanate is C9H6N2O2, and the molecular weight is 174.15 g/mol. (7)

The vapor pressure for toluene 2,4-diisocyanate is 1 mm Hg at 80 C, and it has a log octanol/water partition coefficient (Log Kow) of 0 to 1 (estimated). (7)

Uses
Toluene 2,4-diisocyanate is used as a chemical intermediate in the production of polyurethane products such as foams, coatings, and elastomers. (3) "

"For definition of Groups, see Preamble Evaluation.

VOL.: 71 (1999) (p. 865)
Commercial toluene diisocyanate mixtures
CAS No.: 26471-62-5
Chem. Abstr. Name: 1,3-Diisocyanatomethylbenzene

2,4-Toluene diisocyanate
CAS No.: 584-84-9
Chem. Abstr. Name: 2,4-Diisocyanato-1-methylbenzene

2,6-Toluene diisocyanate
CAS No.: 91-08-7
Chem. Abstr. Name: 1,3-Diisocyanato-2-methylbenzene

5. Summary of Data Reported and Evaluation
5.1 Exposure data
Toluene diisocyanates are industrial chemicals produced in large volumes. Exposure to toluene diisocyanates may occur during their production and in the processing and handling of polyurethane foams.

5.2 Human carcinogenicity data
The risk of cancer associated with occupational exposure to isocyanates has been examined in three industrial cohort studies and in a population-based case-control study of several types of cancer. No strong association or consistent pattern has emerged.

5.3 Experimental data
Commercial mixtures of 2,4- and 2,6-toluene diisocyanates were tested for carcinogenicity in mice and rats by gavage and by inhalation exposure. Administration by gavage induced a dose-related increase in the incidence of subcutaneous fibromas and fibrosarcomas (combined) in male rats, together with an increase in the incidence of pancreatic acinar-cell adenomas in male rats and in pancreatic islet-cell adenomas, neoplastic nodules of the liver and mammary gland fibroadenomas in female rats. In female mice, dose-related increases in the combined incidence of haemangiomas and haemangiosarcomas and of hepatocellular adenomas were observed; no treatment-related tumour was seen in male mice, possibly due to poor survival. No treatment-related tumour was observed after exposure of mice or rats to commercial toluene diisocyanate by inhalation, although the results of the study with rats have not been reported fully.

5.4 Other relevant data
Toluene diisocyanates are metabolized to toluene diamines in humans and rats. Toluene diisocyanates are irritants and respiratory sensitizers in humans and rats.

Toluene diisocyanate did not induce micronuclei in mammalian erythrocytes in vivo. It induced DNA damage and chromosomal aberrations but not sister chromatid exchanges in human lymphocytes in vitro. It induced gene mutation and sister chromatid exchanges but not DNA damage or chromosomal aberrations in rodent cells in vitro. It induced sex-linked mutations in Drosophila and in some experiments was mutagenic in bacteria. The presence of an exogenous metabolic activation system led to inconsistent results, sometimes enhancing and at other times eliminating the genotoxic effects of toluene diisocyanate.

5.5 Evaluation
There is inadequate evidence for the carcinogenicity of toluene diisocyanates in humans.

There is sufficient evidence for the carcinogenicity of toluene diisocyanates in experimental animals.

Overall evaluation
Toluene diisocyanates are possibly carcinogenic to humans (Group 2B).

For definition of the italicized terms, see Preamble Evaluation.

First Published: September 2001
Updated: April 2007

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