Uptake and distribution of 14C during and following inhalation exposure to radioactive toluene diisocyanate.
Inhalation of toluene diisocyanate (TDI) results in toxic responses ranging from pulmonary irritation to immunological sensitization. The use of radioactively labeled isocyanate has made it possible to follow the initial uptake of the compound into the bloodstream independent of the final fate of the isocyanate. This study shows that the rate of uptake into the blood is linear during exposure to concentrations ranging from 0.00005 to 0.146 ppm and that the uptake continues to increase slightly postexposure. It also demonstrates that the radioactivity clears from the bloodstream to a level corresponding to approximately a 100 nM concentration of tolyl group after 72 hr and persists at a nanomolar level even 2 weeks following the exposure. This is similar to the response previously reported by this group for radioactively labeled methyl isocyanate. The initial rate of 14C uptake is also a linear function of the concentration of TDI when expressed either as concentration (ppm) or as concentration multiplied by duration of exposure (ppm.hr). This is discussed in comparison with the toxic responses as a function of both ppm and ppm.hr. Finally, the inclusion of the data on methyl isocyanate indicates that the uptake into arterial blood is a function of exposure concentration, independent of isocyanate structure.
Kennedy
A L
AL
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213.
Stock
M F
MF
Alarie
Y
Y
Brown
W E
WE
D000280:Administration, Inhalation; D000818:Animals; D002250:Carbon Radioisotopes / Q000032:analysis* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003485:Cyanates / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D017953:Isocyanates; D008297:Male; D008657:Metabolic Clearance Rate; D011854:Radiochemistry; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014051:Toluene 2,4-Diisocyanate / Q000097:blood / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D003485:Cyanates; D017953:Isocyanates; D014051:Toluene 2,4-Diisocyanate; C008461:methyl isocyanate