Open AccessUse of the benchmark dose approach for evaluation of dose and time-dependent response to 7-hydroxycoumarin 90-day exposure in rat females
Author(s) -
M.L. Zinovieva,
P.G. Zhminko,
М.Г. Проданчук
Publication year - 2018
Publication title -
ukraïnsʹkij žurnal sučasnih problem toksikologìï/ukraïnsʹkij žurnal sučasnih problem toksikologìï
Language(s) - English
Resource type - Journals
eISSN - 2663-9165
pISSN - 2663-4570
DOI - 10.33273/2663-4570-2018-81-1-17-24
Subject(s) - post hoc , confidence interval , toxicity , reference dose , post hoc analysis , medicine , benchmark (surveying) , mathematics , toxicology , zoology , statistics , risk assessment , computer science , biology , geodesy , geography , computer security
Benchmark dose (BMD) analysis of existing data sets from experimental studies on animal for which NOAEL/LOAEL information is available allows to satisfy the need for quantifiable, scientifically justifiable approach to risk assessment. Previous study of 7-hydroxycoumarin (7-HOC) 3 months toxicity on rats revealed carbohydrates and lipids metabolism disturbance (blood glucose level (BGL) decrease, serum triglyceride level (STL) rise) as biologically relevant parameters to set up NOEL (20 mg/kg).Purpose. To conduct the dose and time of exposure effect dependence comparative analysis of BGL and STL published data set of 7-HOC subchronic toxicity in rats using BMD and NOAEL/LOAEL methodologies.Materials and methods. The available continuous data of STL and BGL from subchronic 7-HOC toxicity study data set for rat females were analyzed by means United States Environmental Protection Agency proposed software, BMDS 2.6.0.1. The response level was set as 10 %.Results. Hill’s model appropriately reflected BGL and STL dependence on 7-HOC dose. The BMDs estimates of STL rise were similar (46–49 mg/kg) in 1, 2, and 3 months of exposure. Coincident dependence was foundfor the lower-bound confidence limits on the BMDs (BMDLs) ranged 21–22 mg/kg at all the studied time points, whereas NOEL for this end point was defined as 50, 20, and 20 mg/kg in 1, 2, and 3 months respectively.BMDs of the BGL decrease were rising with time of exposure amounting 48, 93, 486 mg/kg after 1, 2, and 3 months respectively. BMDLs estimates were 24, 21, 207 mg/kg in 1, 2, and 3 months respectively, while NOEL for this end point were 50, 200, and 200 mg/kg at correspond time points.Conclusion. The benchmark dose method was more powerful statistical tool to analyze 7-HOC effects dose dependence in comparison to traditional approach. The observed BMDs and theirs derivatives changes indicated no enhancement of studied treatment related responses within the exposure time.Key words: benchmark dose approach, 7-hydroxycoumarin, subchronic toxicity.