Format

Send to

Choose Destination
Regul Toxicol Pharmacol. 2015 Mar;71(2):205-12. doi: 10.1016/j.yrtph.2014.12.019. Epub 2014 Dec 31.

Relationship between lethal toxicity in oral administration and injection to mice: effect of exposure routes.

Author information

1
State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin 130117, PR China.
2
State Environmental Protection Key Laboratory of Wetland Ecology and Vegetation Restoration, School of Environment, Northeast Normal University, Changchun, Jilin 130117, PR China. Electronic address: zhaoyh@nenu.edu.cn.

Abstract

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 log1/LD₅₀ between exposure routes.

KEYWORDS:

Absorption; Correlation; Exposure route; Kinetics; Lethal critical concentration; Metabolism

PMID:
25558060
DOI:
10.1016/j.yrtph.2014.12.019
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center