期刊
REGULATORY TOXICOLOGY AND PHARMACOLOGY
卷 71, 期 2, 页码 205-212出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yrtph.2014.12.019
关键词
Exposure route; Correlation; Lethal critical concentration; Absorption; Kinetics; Metabolism
资金
- National Natural Science Foundation of China [21377022]
- National Training Programs of Innovation and Entrepreneurship for Undergraduates of China [201410200081]
The lethal toxicity (LD50) in oral administration, intravenous, intraperitoneal, intramuscular and subcutaneous injections were used to investigate relationships of log 1/LD50 from different exposure routes. Regression analysis showed that log 1/LD50 in oral route was related to the toxicity in injection route. This relationship in lethality between the two routes is apparently due to the same mechanisms of the compounds to the same species. However, the scatter in the correlation curve indicates that exposure route is an important factor that influences the relationship. Some compounds with low intestinal absorption exhibit much less toxicity in oral administration than that in the injection route. A systemic bias of log 1/LD50 between oral and injection routes indicates that tissue distribution of compounds between blood and target site is a very rapid process, leading to log 1/LD50 in injection greater than those in oral administration. Although compounds can be metabolized in the body both from oral and injection routes, first-pass metabolism occurs in oral route but not in injection route. This will result in decrease of toxicity in oral route for most compounds as compared with injection route. In addition, experimental uncertainty, differences in gender, and species can also affect relationships of log 1/LD50 between exposure routes. (C) 2014 Elsevier Inc. All rights reserved.
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