Urinary excretion of toluene diisocyanates in rats following dermal exposure.
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 h 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 h.
Yeh
Hui-Jung
HJ
Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Lin
Wei-Chao
WC
Shih
Tung-Sheng
TS
Tsai
Perng-Jy
PJ
Wang
Shan-Tair
ST
Chang
Ho-Yuan
HY
D000279:Administration, Cutaneous; D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects*; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine
D004785:Environmental Pollutants; D014051:Toluene 2,4-Diisocyanate; C026942:2,6-diisocyanatotoluene