Risk assessment dosimetry model for inhaled particulate matter: II. Laboratory surrogates (rat).
Inhalation toxicology investigations are often performed with laboratory animals to address the potential health effects of inhaled air pollutants on human beings. In Part II of this risk assessment study we have considered the deposition of inhaled particulate matter in the laboratory rat as the surrogate of choice. Calculations were performed in an analogous manner to those conducted in Part I for human subjects. To simulate a wide range of human respiratory intensities associated with different levels of physical activities that must be recognized in the determination of air pollution standards, the CO(2) concentrations within animal inhalation exposure chambers may be controlled. Accordingly, we have regulated rat breathing parameters to correspond to a range of human activities, from rest to work. The results of this interspecies modeling study have been presented in a variety of graphical formats to ease comparisons with findings from experiments and to facilitate integration of the results into risk assessment analyses. The findings of our work clearly demonstrate that interspecies simulations can be employed to design animal tests a priori so that the results can be effectively and efficiently extrapolated to human conditions in a meaningful manner.
Martonen
Ted B
TB
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Mail Drop 74, 86 T.W. Alexander Drive, Research Triangle Park, NC 27711, USA. martonen.ted@epa.gov
Schroeter
Jeffry D
JD
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000009:adverse effects* / Q000493:pharmacokinetics; D000818:Animals; D002245:Carbon Dioxide / Q000032:analysis; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019570:Inhalation Exposure; D008954:Models, Biological; D010316:Particle Size; D051381:Rats; D012119:Respiration; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism; D018570:Risk Assessment; D013045:Species Specificity; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D017155:Wettability
D000393:Air Pollutants; D014028:Tobacco Smoke Pollution; D002245:Carbon Dioxide