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  • Title: Concentration-dependent elicitation of dermal sensitization in guinea pigs treated with 2,4-toluene diisocyanate.
    Author: Koschier FJ, Burden EJ, Brunkhorst CS, Friedman MA.
    Journal: Toxicol Appl Pharmacol; 1983 Mar 15; 67(3):401-7. PubMed ID: 6302947.
    Abstract:
    2,4-Toluene diisocyanate (TDI) can cause pulmonary sensitization and allergic skin reactions. Since many commercial materials contain TDI, the present study was designed to determine the concentration-dependent elicitation of dermal sensitization in guinea pigs treated with TDI. Young adult guinea pigs received two open, epicutaneous induction applications (25 microliters) of 8,20, or 40% TDI in n-butyl ether on two separate areas. Five days later, animals were challenged with 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4% TDI (25 microliter per concentration site). All challenge applications except the 0.0% solution elicited a positive response in 75 to 100% of the animals, and the severity of the skin reactions was dependent on the concentrations of the challenge and induction application. In another study at lower doses, animals received a total induction application (25 microliters per each of two sites) of either 4 or 8% TDI and were challenged with 0.0, 0.006, 0.012, 0.025, 0.05, and 0.1% of TDI (25 microliters per site). TDI did not elicit a sensitization response at challenge concentrations up to 0.012% (total application of 3 micrograms) when a 4% induction application was used, while a challenge concentration of 0.025% (total application of 6.25 micrograms) elicited a sensitization response in 63% of the animals. At the 8% induction application (total application of 4000 micrograms), all challenges, except the 0.0% indicated sensitization, and the intensities of the skin reactions were correlated with the challenge concentrations and the induction application. In conclusion, the results demonstrate that TDI produced sensitization at dilute induction concentrations and that the severity of the dermal response was correlated with the concentration used at induction and challenge. Furthermore, no observed effect levels were determined below which the challenge concentration did not elicit a dermal hypersensitivity reaction. When 4% TDI was applied at induction, no observed effect was seen with a dermal challenge application of 3 micrograms whereas an effect was seen with 6.25 micrograms (in 25 microliters) when n-butyl ether was the solvent.
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