What dangerous dose Tolylene-2,4-diisocyanate have?

　　Tolylene-2,4-diisocyanate is primarily used as a chemical intermediate in the production of polyurenthane products. Tolylene-2,4-diisocyanate is extremely toxic from acute (short-term) and chronic (long-term) exposures. Acute exposure to high levels of Tolylene-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 (CNS). Chronic inhalation exposure to Tolylene-2,4-diisocyanate in humans has resulted in significant decreases in lung function in workers, an asthma-like reaction characterized by wheezing, dyspnea, and bronchial constriction. Animal studies have reported significantly increased incidences of tumors of the pancreas, liver, and mammary glands from exposure to Tolylene-2,4-diisocyanate via gavage (experimentally placing the chemical in the stomach). The International Agency for Research on Cancer (IARC) has classified Tolylene-2,4-diisocyanate as a Group 2B, possible human carcinogen.

Tolylene-2,4-diisocyanate,584-84-9

　　1.Acute Effects

　　*Acute exposure to high levels of Tolylene-2,4-diisocyanate in humans, via inhalation, results in severe irritation of the skin, eyes, and nose, and causes nausea and vomiting.

　　*Acute animal tests in rats have shown Tolylene-2,4-diisocyanate to have moderate to extreme acute toxicity from inhalation exposure and low acute toxicity from oral exposure.

　　2.Chronic Effects (Noncancer)

　　*Chronic inhalation exposure to Tolylene-2,4-diisocyanate in workers has caused significant decreases in lung function, an asthma-like reaction characterized by wheezing, dyspnea, and bronchial constriction.

　　*Animal studies have reported irritation of respiratory tissues, bronchopneumonia, and weight loss from chronic exposure to Tolylene-2,4-diisocyanate.

　　*EPA has not established a Reference Concentration (RfC) or a Reference Dose (RfD) for Tolylene-2,4-diisocyanate. However, EPA has established an RfC of 0.00007 milligrams per cubic meter (mg/m3) for the mixture of toluene 2,4- and 2,6-diisocyanate based on respiratory effects in humans. The RfC is an estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups), that is likely to be without appreciable risk of deleterious noncancer effects during a lifetime. It is not a direct estimator of risk but rather a reference point to gauge the potential effects. At exposures increasingly greater than the RfC, the potential for adverse health effects increases. Lifetime exposure above the RfC does not imply that an adverse health effect would necessarily occur.

　　*EPA has medium confidence in the study on which the RfC was based. Although the study was prospective and used appropriate endpoints and state-of-the-art methods in monitoring, the lack of exposure characterization in the first 2 years and the unknown relationship of peak exposures to lung function decline detract from clear identification of the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL); medium confidence in the database because of limitations in monitoring and analytical procedures in the majority of occupational studies cited and the uncertainties associated with peak vs. time-weighted-average (TWA) exposures as determinants of toxicity and, in addition, developmental toxicity data from a second species are lacking; and consequently medium confidence in the RfC.

　　3.Reproductive/Developmental Effects

　　*No information is available on the reproductive or developmental effects of Tolylene-2,4-diisocyanate in humans.

　　*No reproductive or developmental effects were observed in rats exposed to a mixture of toluene 2,4- and 2,6-diisocyanate via inhalation.